Indian Patents. 229191:A PROCESS FOR PREPARATION OF PHARMACEUTICAL COMPOSITIONS AND CONTROLLED RELEASE DRUG DELIVERY SYSTEMS BASED ON NOVEL POLYSACCHARIDE EXCIPIENT(HUPU GUM)

Title of Invention	A PROCESS FOR PREPARATION OF PHARMACEUTICAL COMPOSITIONS AND CONTROLLED RELEASE DRUG DELIVERY SYSTEMS BASED ON NOVEL POLYSACCHARIDE EXCIPIENT(HUPU GUM)
Abstract	Compositions comprising Hupu gum as a novel excipient in pharmaceuticals, neutraceuticals and cosmeceuticals in general and controlled release tablets of freely soluble drugs like Diltiazem hydrochloride, partially soluble drugs like Rifampicin, sparingly soluble drugs like Diclofenac Sodium in particular is disclosed herein.

Full Text	Field of the invention: The present invention relates to a process for the preparation of compositions containing Hupu gum a novel excipient in pharmaceuticals, neutraceuticals and cosmeceuticals in general and for controlled release tablets of freely soluble drugs like Diltiazem hydrochloride, partially soluble drugs like Rifampicin, and sparingly soluble drugs like Diclofenac Sodium in particular. Hupu gum efficiently retarded the release of above mentioned drugs; it is seen justifying the novelty of the compositions where Hupu gum is incorporated as an excipient in controlled drug delivery system, which will drastically reduce the prices of the commercially available formulations. Process for preparation of pharamaceutical composition and controlled release drug delivery systems containing a novel polysaccharides excipient, Hupu gum is claimed by us as being highly efficient and economic. Background and prior art: Hupu (Kondagogu or Kolha) gum is the dried gummy exudates obtained from the deciduous tree of 'Cochlospermum religious". Family Cochlosermaceae, (Synonym C gossypium D.C.) abundantly found in hills and forests of Chittor District in Andhra Pradesh. Cochlospermaceae, gossypium is also found in South and North America and is described in Germplasm Resources Information Nature of Agricultural Research Service (www.ars.grin.qov). As per Botanica Systematica-2002, this plant has been reclassified as belonging to Bixaceae family. Bark of this plant is found to have the healing properties of bum injuries, broken limbs of cattle and also used in sores and T.B. Reports on toxicity studies on the Hupu gum revealed that the gum had no toxic effects and can be safely used as a food additive. A thorough literature survey showed that there are no reports on the use of Hupu gum as an excipient. The available reports on Hupu gum are sub chronic toxicity studies on rats, physico chemical analysis and reproductive ecology of Cochlospermum religiosum. No toxicity was reported, when Hupu gum was fed onto the rats even up to 5% w/w concentration for a period of 90 days. Natural polysaccharides and their derivatives represent a group of polymers widely used in pharmaceutical dosage form. Various kinds of natural gums are used in the food industry and are regarded as safe for human consumption. Natural gums are often preferred to synthetic materials due to their non-toxicity, low cost and free availability. It should be noted that many "old" materials compete successfully today after almost a century of efforts to replace them. It is the usual balance of economics and performance that determines the commercial realities. Natural gums have been modified to overcome certain drawbacks like uncontrolled rate of hydration, thickening, and drop in viscosity on storage, microbial contamination and the like. The use of controlled release technology in the formulation of pharmaceutical products has become increasingly important in the last several years either to achieve the desired level of therapeutic activity required for a new drug entity or to expand the life cycle of an existing drug through improved performance or patient compliance. Drug release from these systems should be at a desired, predictable and reproducible rate. These goals cannot be achieved without the using proper excipients, as the modification of the existing drug to achieve this is very difficult. Controlled release drug delivery systems have been designed for oral, parenteral, implantation and transdermal routes. Majority of the drug delivery systems available in the market are oral drug delivery systems due to their obvious advantages of ease of administration and patient compliance. In the design of these drug delivery systems, excipients play an important role. Excipients from various sources like natural, synthetic, semi - synthetic are generally used in the design of controlled release dosage forms. Summary of the invention: The present invention relates to a process for the preparation of compositions containing Hupu gum a novel excipient in pharmaceuticals, neutraceuticals and cosmeceuticals in general and controlled release tablets of freely soluble drugs like Diltiazem hydrochloride, partially soluble drugs like Rifampicin, sparingly soluble drugs like Diclofenac Sodium in particular. Hupu gum efficiently retarded the release of above mentioned drugs; it is seen justifying the novelty of the compositions where Hupu gum is incorporated as an excipient in controlled drug delivery system, which will drastically reduce the prices of the commercially available formulations. Process for preparation of pharamaceutical composition and controlled release drug delivery systems containing a novel polysaccharides excipient, Hupu gum is claimed by us as being highly efficient and economic. Detailed description: Hupu gum was evaluated for its physico-chemical and micromeritic properties and microbial load of the gum. Preparation of the Hupu gum: The gum is available as transparent pale yellow colored lumps having characteristic slight salty taste. These lumps were crushed to powder using a laboratory scale grinder. The resulting powder is passed through mesh # 100. The powder collected was used for further studies. Characterization of Hupu gum: Flow properties of powder are very important in the pre-formulation studies for the preparation of tablets and capsules. The flow properties of the powders can be predicted from the values of bulk density, bulkiness, tapped density, angle of repose, compressibility index and Hausner index. Hupu gum was evaluated for its pH, swelling index, water absorption properties and visco elastic properties. The results are shown in Table 1. It was subjected to thermal analysis by DSC. Microbial load of the Hupu gum: Hupu gum was tested for microbial burden immediately after its receipt and results are showed in the Table 2. The results of true density, bulk density, bulkiness, angle of repose, compressibility index, Hausner index, pH and viscosity of HG are given in Table 1. The values of tapped density, bulk density, compressibility index and angle of repose exhibited by Hupu gum clearly indicated that Hupu gum had good flow properties and was suitable for direct compression. The pH of 1% w/v solution of Hupu gum was found to be 4.9 indicating that gum is slightly acidic in nature. High value of swelling index indicated the high swelling ability of the carrier. Visco elastic properties of Hupu gum revealed that it followed pseudo plasticity. DSC thermogram of Hupu gum exhibited a broad endothermic peak at 98.9°C, owing to its amorphous character. Preparation of Hupu gum matrix tablets of Rifampicin and their evaluation: Rifampicin, a semi synthetic hydrazine derivative of rifamycin B, one of the most potent and powerful mycobactericidal drugs is used mainly in intermittent therapy, both in tuberculosis and leprosy, because of its high cost and adverse side effects. Chemically it is designated as (12Z, 14E, 24EH2S, 16S, 17S, 18R, 19R, 20R, 21S, 22R, 23S)-l,2-dihydro-5, 6, 9, 17, 19 -pentahydroxy - 23 - methoxy - 2,4, 12, 16, 18, 20, 22-heptamethyl-8-(4-methyl piperazin-1-yliminomethyl)-l,l l-dioxo-2,7(epoxy-pentadeca-l,l l,13-trienimino)aphtha[2,l-b] furan-21-yl acetate, which is produced by a strain of Streptomyces mediterranei. Drug passed through mesh # lOOwas used in the present study. Methods of analysis used in present investigation The methods available for the estimation of Rifampicin are briefly reviewed here. Spectrophotometric method based on the measurement of absorbance of solution of Rifampicin in pH 7.4 phosphate buffer at 475 nm was official in LP., B.P. and U.S.P. The method reported in the Indian Pharmacopoeia 1996 was used in the present study with a minor modification. Method described in the LP. used pH 7.4 phosphate buffer for the preparation of standard solutions whereas in the present study 0.02% w/v of ascorbic acid was also added to prevent the decomposition of soluble Rifampicin. PREPARATION OF HUPU GUM MATRIX TABLETS Direct compression method: The drug and the Hupu gum sufficient for a batch of 100 tablets, as shown in Table 3, were passed through mesh 100, mixed thoroughly with aerosil and passed through mesh 40 to ensure complete mixing. Then the blend was lubricated with magnesium stearate. Tablets containing Rifampicin equivalent to 300mg were compressed using 13 mm flat round punches on 16 station Cadmach Rotary Compression Machine. Compression force of the machine was adjusted to obtain hardness in the range of 5-6 Kg/cm . Aerosil was used in the formulations to enhance the flow properties of final blend. Estimation of drug content: From each batch of prepared tablets, five tablets were randomly collected and powdered. A quantity of powder equivalent to 100 mg was transferred into a 100 ml volumetric flask, sufficient amount of methanol was added to produce 100 ml. Shaken for 20 minutes and filtered. Diluted 2 ml of the filtrate to 100 ml with pH 7.4 phosphate buffer containing ascorbic acid and assayed for the drug content by the method described earlier. Differential Scanning Calorimetry (DSC): Differential Scanning Calorimetry of Rifampicin and Rifampicin-Hupu gum compressed tablet was performed in the temperature range of 30°C to 300°C using Shimadzu DSC-50 thermal analyzer under static air atmosphere. Samples were placed in an aluminium pan and heated at a rate of 10°C/minute with an empty pan as reference. Infrared spectroscopy (IR): Infrared spectra of the pure Rifampicin and Rifampicin contained Hupu gum matrix were determined from mineral acid mull using PERKIN-ELMER 841 IR spectrophotometer. The scanning range used was 4000 to 600 cm"^ In vitro dissolution studies: Dissolution test was carried out using USP XXIV type-I (Basket) dissolution rate test apparatus (model DISSO 2000, M/s, Labindia). The stirring rate was 100 rpm. The pH 7.4 phosphate buffer containing ascorbic acid (200 )u,g/ml) was used as dissolution medium (900 ml) and was maintained at 37 ± 0.5°C. Samples of 5 ml were withdrawn at predetermined time intervals with syringe fitted with a filter. The collected samples were diluted suitably, wherever necessary and were analyzed for the Rifampicin content by spectrophotometric method at 475 nm. The volume withdrawn at each time interval was replaced with fresh quantity of 5 ml of dissolution medium. Each dissolution study was performed for three times and mean values taken were reported. At the end of 12 hrs of dissolution testing, the tablet remains were collected from the basket by thorough washing with methanol into a 100ml volumetric flask for estimation of the remaining drug content. The volume was made up to 100ml with methanol. Suitable dilutions were made with pH 7.4 phosphate buffer and remaining drug content was assayed. This is to make sure that the amount of drug remaining adds to the drug release to give total mass balance of drug content. Other tests like weight variation, hardness, friability etc. were carried out and the resuhs are found to be satisfactory and with in the limits. Effect of Channeling Agents on Rifampicin Release Kinetics: Various channeling agents like Mannitol (RIF-T300-F007A-C), Sorbitol (RIF-T300-F008A-C), Lactose (RIF-T300-F009A-C), Dextrose (RIF-T300-F010A-C) were studied on the release pattern of Rifampicin matrix tablets in different concentrations like 5%, 10%, 15%. The Formulation RIF-T300-F004 was selected and the various concentrations of channeling agents were added and evaluated for their in vitro dissolution release pattern and subjected to assay, IR, DSC studies. The in vitro dissolution studies of the prepared tablets revealed that the Hupu gum behaved differently depending on the proportions used in the tablet preparation as shown in Fig.l. Generally, in hydrophilic matrix controlled release tablets, initial burst release is observed due to two factors. If the surface area of the polymer is not large enough to cover the drug particle at the surface of the matrix, there is a great chance of burst effect in drug release. Secondly, if the polymer does not hydrate quickly, the surface barrier cannot be formed immediately, which may cause a large portion of drug to be released during the initial phase of release profile. Thus, the surface area as well as the hydration rate of the polymer can play an important role in drug release from matrix tablets, especially at the beginning of the release profile. That quick hydration and subsequent gel formation are foremost and important properties of an excipient for it to be used for controlled release formulation. In Hupu gum matrix tablets, there was no initial bursting effect due to its quick hydration and immediate formation of gel structure around the tablet. The influence of compression force on release kinetics is not very important for hydrophilic matrices, however, this fact is only observed from compression force adequate to prevent the partial or total matrix disintegration. In the present work the compression force of the tablet machine was so adjusted that made it possible to obtain tablets whose hardness level was between 5-6 kg/cm . The weight variations of the tablets were within the Pharmacopoeial limits (not more than two of the 20 tablets differ from the average weight by more than 5% and no tablet differs by more than 10%). The release rate constants revealed that the release rate increased as the proportion of Hupu gum decreased and followed first order release kinetics. In order to establish the mechanism of drug release, the experimental data were fitted to the exponential equation (MJ/MQ^ = Kt"). The linear correlation coefficients of the slopes and slope values shown indicated that the release kinetics confirm predominantly to non- fickian diffusion (i.e. square root of time profile). This classical Higuchi type of release mechanism can be explained as a result of the rapid hydration of the polymer molecules on the surface of the tablets, which results in a gel or a highly viscous solution surrounding the matrix that restricts water penetration into the center. The net result is a reduction of the rate of drug release as a function of time. This was confirmed by the linearity of the plot obtained when cumulative amount of drug released was plotted as a function of square root of time (t'^')- The DSC thermograms revealed that there is no interaction or complexation occurred between Rifampicin and Hupu gum during the manufacturing process. The channeling agents when in contact with the dissolution fluid immediately dissolves and creates channels in the matrix tablets and there by enhanced the release of Rifampicin. The channeling agents mannitol, sorbitol, lactose, dextrose significantly enhanced the release of Rifampicin from the selected formulation RIF-T300-F004. No significant difference in release rate was observed up to 5% concentration of channeling agents. At 10% concentration Sorbitol and Dextrose increased the Rifampicin release whereas with Mannitol and lactose no significant increment in Rifampicin release rate. At 15% concentration significant enhancement in release of Rifampicin was observed. Beyond the concentration 15% of channeling agents, the hardness of the tablets was reduced and prone for higher friability values. Among the studied channeling agents Sorbitol was found to increase the release of Rifampicin to 88% from 28% at the end of 12hrs. Release rate followed first order kinetics and by non-fickian diffusion mechanism. The effect of channeling agent was in the order of Sorbitol > Dextrose > Lactose > Mannitol (Fig.2-5). Preparation of Hupu Gum Matrix Tablets of Diclofenac Sodium and their Evaluation: In the next phase Hupu gum matrix tablets were prepared with Diclofenac sodium. Diclofenac sodium (DS), a substituted phenyl-acetic acid derivative, designated chemically as 2-[(2,6-dichlorophenyl)-amino]-benzene acetic acid mono sodium salt. It is a nonsteroidal anti-inflammatory drug (NSAID) widely used in the management of many inflammatory conditions. In addition to its anti-inflammatory effect, DS has analgesic and anti-pyretic action. It is official in Indian Pharmacopoeia (IP), British Pharmacopoeia (BP) and United States Pharmacopoeia (USP). Diclofenac sodium is a white or slightly yellowish, slightly hygroscopic, crystalline powder. It is acidic in nature, freely soluble in methanol, soluble in ethanol and is sparingly soluble in water. The reported solubility in water is 36 mg/ml^ Method of Analysis Used in Present Investigation A spectrophotometric method based on the measurement of absorbance at 275 nm in phosphate buffer (pH 7.4) was used in the present study for the estimation of Diclofenac sodium from the samples. Preparation ofHupu Gum Matrix Tablets of Diclofenac Sodium Wet granulation method The drug and different proportions of Hupu gum as shown in Table 4, sufficient for a batch of 100 tablets were passed through a 100 No. Sieve and thoroughly mixed to ensure complete mixing and granulated with 70% Isopropyl alcohol. The wet mass was dried in a hot air oven at not more that 50°C until LOD (Loss on drying) reaches with in 2-3%. Dried granules were lubricated with mesh 40 passed Mg stearate and stored in a tightly packed container. Tablets containing Diclofenac sodium equivalent to lOOmg were compressed using 9 mm, slightly concave round punches on 16 stations Cadmach rotary compression machine. Compression force of the machine was adjusted to obtain hardness in the range of 5-6 Kg/cml In vitro dissolution studies: Dissolution test was carried out using USP XXIV type-I (Basket) dissolution rate test apparatus (model DISSO 2000, M/S Labindia) at 100 rpm. The pH 7.4 phosphate buffer was used as dissolution medium (900 ml) and was maintained at 37 ± 0.5^C. Samples of 5 ml were withdrawn at predetermined time and were analyzed for the Diclofenac sodium content by spectrophotometric method at 275 nm. Each dissolution study was performed for three times and mean values taken were reported. Preparation of Hupu Gum Matrix Tablets of Diltiazem Hydrochloride and their Evaluation Hupu gum matrix tablets were prepared with Diltiazem Hydrochloride. Diltiazem hydrochloride is (+)-5-[2-(dimethylamino)ethyl]-cis, 2,3dihydro- 3-hydroxy-2-(p" methoxyphenyl)"l,5-benzo-thia2epin-4(5H)-one acetate monohydrochloride. It is an important coronary vasodilator drug of the calcium channel-blocker, used in the therapy of heart disease and hypertension. The compound also exhibits weak negative inotropic and chronotropic actions as well as a weak hypotensive activity Method of Analysis Used in Present Investigation A spectrophotometric method based on the measurement of absorbance at 238 nm in Distilled water was used in the present study for the estimation of Diltiazem Hcl from the samples. Preparation ofHupu Gum Matrix Tablets of Diltiazem hydrochloride Wet granulation method The drug and different proportions of Hupu gum shown in Table 5, sufficient for a batch of 100 tablets were passed through a 100 No. Sieve and thoroughly mixed to ensure complete mixing and granulated with 70% Isopropyl alcohol. The wet mass was dried in a hot air oven at not more that SOT until LOD (Loss on drying) reaches with in 2-3%. Dried granules were lubricated and stored in a tightly packed container. Tablets containing Diltiazem hydrochloride equivalent to 90mg were compressed using 9 mm, slightly concave round punches on 16 stations Cadmach rotary compression machine. Compression force of the machine was adjusted to obtain hardness in the range of 5-6 kg /Cm^. In vitro dissolution studies: Dissolution test was carried out using USP XXIV type-I (Basket) dissolution rate test apparatus (model DISSO 2000, M/S Labindia) at 100 rpm. Distilled water used as dissolution medium (900 ml) and was maintained at 37 ± 0.5°C. Samples of 5 ml were withdrawn at predetermined time intervals and were analyzed for the Diltiazem HCl content by spectrophotometric method at 238nm. Each dissolution study was performed for three times and mean values taken were reported. Dissolution profiles of prepared Diclofenac sodium formulations were showed in the Fig.6 where as dissolution profile of Diltiazem HCl were showed in Fig.7. Release kinetics of Diclofenac sodium and Diltiazem HCl were followed first order kinetics and the release kinetics conforms predominantly to non- fickian diffusion (i.e. square root of time profile). This classical Higuchi type of release mechanism can be explained as a result of the rapid hydration of the polymer molecules on the surface of the tablets, which results in a gel or a highly viscous solution surrounding the matrix that restricts water penetration into the center. The net result is a reduction of the rate of drug release as a function of time. Detailed Description of Drawings: Fig.l illustrates describes the dissolution profiles of Rifampicin from Hupu gum matrix formulations. In Fig.l, numbers 1-6 represents different formulation codes containing different Hupu gum concentrations which are RIF-T300- FOOl, RIF-T300-F002, RIF-3000-F003, RIF-T300-F004, RIF-300-F005 and RIF-300-F006 respectively. 7 represents X- axis which denotes time in hours and 8 represents Y-axis which denotes cumulative percent drug released. Fig.l reveals that Hupu gum behaved differently depending on the proportions used in the formulations. Fig.2 describes the effect of channeling agent, mannitol on the formulation code of Rifampicin, RIF- T300-F004. In Fig .2, numbers 9-12 represents different formulation codes containing mannitol in different concentrations such as 0, 5, 10, and 15%, RIF- T300-F004, RIF.T300-F007A, RIF-T300-F007B, RIF-300-F007C respectively. From the Fig.2 it is come to know that 15% concentration of the channeling agent in the formulation has increased the drug release. 13 denotes X- axis which is time in hours, and 14 denotes Y- axis which is percent release of the drug. Fig.3 describes the effect of channeling agent sorbitol in the formulafion code of Rifampicin RIF-300-F004, In Fig .3, numbers 15-18 represents different formulation codes containing sorbitol in different concentrations, RIF- T300-F004, RIF-T300-F008A, RIF-T300-F008B, RIF-300-F008C respectively. Fig.3 shows that 15% concentration of the channeling agent in the formulation has increased the drug release. 19 denotes X- axis which is time in hours, and 20 denotes Y- axis which is percent release of the drug. Fig.4 describes the effect of channeling agent lactose in the formulation code of Rifampicin RIF-300-F004. In Fig .4, numbers 21-24 represents different formulation codes containing lactose in different concentrations, RIF- T300-F004, RIF-T300-F009A, RIF-T300-F009B, RIF-300-F009C respectively. Fig.4 shows that 15% concentration of the channeling agent in the formulation has increased the drug release. 25 denotes X- axis which is time in hours, and 26 denotes Y- axis which is percent release of the drug. Fig.5 describes the effect of channeling agent dextrose in the formulation code of Rifampicin RIF-300-F004, In Fig .5, numbers 27-30 represents different formulation codes containing dextrose in different concentrations, RIF- T300-F004, RIF-T300-F0010A, RIF-T300-FOOIOB, RIF-300-F0010C respectively. Fig.5 illustrates that it is come to know that 15% concentration of the channeling agent in the formulation has increased the drug release. 31 denotes X- axis which is time in hours, and 32 denotes Y- axis which is percent release of the drug. Fig.6 describes the dissolution profiles of Diclofenac sodium from Hupu gum matrix formulations. In Fig.6, numbers 33-36 represents different formulation codes containing different Hupu gum concentrations, DFS-T-100-FOOl, DFS-T100-F002, DFS-T100-F003, DFS-T100-F004, respectively. 37 denote X- axis which is time in hours and 38 denotes Y-axis which is cumulative percent drug released. Fig.6 reveals that Hupu gum behaved differently depending on the proportions used in the formulations. Release kinetics showed first order kinetics and confirms predominantly to non- fickian diffusion. Fig.7 describes the dissolution profiles of Diltiazem hydrochloride from Hupu gum matrix formulations. In Fig.7, numbers 39-42 represents different formulation codes containing different Hupu gum concentrations, DIL-T-90-F001, DIL-T90-F002, DIL-T90-F003, DIL-T90-F004, respectively. 39 denotes X- axis which is time in hours and 40 denotes Y-axis which is cumulative percent drug released. Fig.7 reveals that Hupu gum behaved differently depending on the proportions used in the formulations. Release kinetics showed first order kinetics and confirms predominantly to non- fickian diffusion. While the present invention is described above in connection with preferred or illustrative embodiments, these embodiments are not intended to be exhaustive or limiting of the invention. Rather, the invention is intended to cover all alternatives, modifications and equivalents included within its scope. Form the above studies, it can be concluded that Hupu gum could be efficiently used as sustained release excipient in wet granulation as well as direct compression techniques for the various classes of drugs like freely soluble, partially soluble and slightly soluble drugs in the design of controlled drug delivery systems. I claim, 1. The process for preparation of novel pharmaceutical compositions for controlled release drug delivery systems comprising novel poly saccharide excipient (Hupu gum) and an active agent, wherein said process comprises; Mixing of drug and Hupu gum; passing through 100 mesh; mixing thoroughly with aerosil; passing through 40 mesh to ensure uniform mixing; lubricating the blend with magnesium stearate and compressing into tablets. 2. The process as claimed in claim 1, wherein the said drug is selected from partially soluble drug such as Rifampicin. 3. The process as claimed in claim 1, wherein the said aerocil is used to increase the flow properties of the blend. 4. The process as claimed in claim 1, wherein the said process is direct compression. 5. The process as claimed in claim 1, wherein the said process is used to prepare controlled release drug delivery systems by using novel excipient Hupu gum. 6. The process as claimed in claim 1, wherein the said process is used to prepare sustained release drug delivery systems by using novel excipient Hupu gum 7. The process as claimed in claim 1, wherein the said process is used to prepare modified release drug delivery systems by using novel excipient Hupu gum. 8. The process as claimed in claim 1, wherein the said process is used to prepare delayed release drug delivery systems by using novel excipient Hupu gum. 9. The process for preparation of novel pharmaceutical compositions for controlled release drug delivery systems comprising as an excipient (Hupu gum) and an active agent, wherein the said process comprises, Mixing of drug and Hupu gum; passing through 100 mesh; mixing thoroughly; granulating with 70%isopropyl alcohol; drying the wet mass in hot air oven at not more than that 50°C until LOD reaches within 2-3%;lubricating the dried granules with 40 mesh magnesium stearate and compressing said lubricate into tablet with tablet punches. 10. The process as claimed in claim 9, wherein said drug is selected from freely soluble drugs like Diltiazem hydrochloride and sparingly soluble drugs like Diclofenac sodium. 11. The process as claimed in claim 9, wherein said drug is Diltiazem hydrochloride. 12. The process as claimed in claim 9, wherein said drug is Diclofenac sodium. 13. The process as claimed in claim 9, wherein said process is wet granulation. 14. The process as claimed in claim 9, wherein said process is used to prepare controlled release drug delivery systems by using novel excipient Hupu gum. 15. The process as claimed in claim 9, wherein said process is used to prepare sustained release drug delivery systems by using novel excipient Hupu gum 16. The process as claimed in claim 9, wherein said process is used to prepare modified release drug delivery systems by using novel excipient Hupu gum. 17. The process as claimed in claim 9, wherein said process is used to prepare delayed release drug delivery systems by using novel excipient Hupu gum. 18. The process for preparation of novel pharmaceutical composition for controlled release drug delivery system as claimed in claim 1 and 9, wherein the said Hupu gum is prepared by a method comprising; crushing the pale yellow colored lumps into powder using a laboratory scale grinder; passing through 100 mesh and collecting the powder. 19. The process for preparation of novel pharmaceutical composition and controlled release drug delivery systems wherein, that there is no interaction or complexation occurred between Rifampicin and Hupu gum during the manufacturing process. 20. The process for preparation of novel pharmaceutical composition and controlled release drug delivery systems comprising a novel excipient Hupu gum as substantially described herein with reference to the foregoing examples 1 to3.

Full Text

Field of the invention:
The present invention relates to a process for the preparation of compositions containing Hupu gum a novel excipient in pharmaceuticals, neutraceuticals and cosmeceuticals in general and for controlled release tablets of freely soluble drugs like Diltiazem hydrochloride, partially soluble drugs like Rifampicin, and sparingly soluble drugs like Diclofenac Sodium in particular.
Hupu gum efficiently retarded the release of above mentioned drugs; it is seen justifying the novelty of the compositions where Hupu gum is incorporated as an excipient in controlled drug delivery system, which will drastically reduce the prices of the commercially available formulations. Process for preparation of pharamaceutical composition and controlled release drug delivery systems containing a novel polysaccharides excipient, Hupu gum is claimed by us as being highly efficient and economic.
Background and prior art:
Hupu (Kondagogu or Kolha) gum is the dried gummy exudates obtained from the deciduous tree of 'Cochlospermum religious". Family Cochlosermaceae, (Synonym C gossypium D.C.) abundantly found in hills and forests of Chittor District in Andhra Pradesh.
Cochlospermaceae, gossypium is also found in South and North America and is described in Germplasm Resources Information Nature of Agricultural Research Service (www.ars.grin.qov). As per Botanica Systematica-2002, this plant has been reclassified as belonging to Bixaceae family. Bark of this plant is found to have the healing properties of bum injuries, broken limbs of cattle and also used in sores and T.B. Reports on toxicity studies on the Hupu gum revealed that the gum had no toxic effects and can be safely used as a food additive.
A thorough literature survey showed that there are no reports on the use of Hupu gum as an excipient. The available reports on Hupu gum are sub chronic toxicity studies on rats, physico chemical analysis and reproductive ecology of Cochlospermum religiosum. No

toxicity was reported, when Hupu gum was fed onto the rats even up to 5% w/w concentration for a period of 90 days.
Natural polysaccharides and their derivatives represent a group of polymers widely used in pharmaceutical dosage form. Various kinds of natural gums are used in the food industry and are regarded as safe for human consumption. Natural gums are often preferred to synthetic materials due to their non-toxicity, low cost and free availability. It should be noted that many "old" materials compete successfully today after almost a century of efforts to replace them. It is the usual balance of economics and performance that determines the commercial realities. Natural gums have been modified to overcome certain drawbacks like uncontrolled rate of hydration, thickening, and drop in viscosity on storage, microbial contamination and the like.
The use of controlled release technology in the formulation of pharmaceutical products has become increasingly important in the last several years either to achieve the desired level of therapeutic activity required for a new drug entity or to expand the life cycle of an existing drug through improved performance or patient compliance. Drug release from these systems should be at a desired, predictable and reproducible rate. These goals cannot be achieved without the using proper excipients, as the modification of the existing drug to achieve this is very difficult.
Controlled release drug delivery systems have been designed for oral, parenteral, implantation and transdermal routes. Majority of the drug delivery systems available in the market are oral drug delivery systems due to their obvious advantages of ease of administration and patient compliance. In the design of these drug delivery systems, excipients play an important role. Excipients from various sources like natural, synthetic, semi - synthetic are generally used in the design of controlled release dosage forms.
Summary of the invention:
The present invention relates to a process for the preparation of compositions containing Hupu gum a novel excipient in pharmaceuticals, neutraceuticals and cosmeceuticals in general and controlled release tablets of freely soluble drugs like Diltiazem hydrochloride,

partially soluble drugs like Rifampicin, sparingly soluble drugs like Diclofenac Sodium in particular.
Hupu gum efficiently retarded the release of above mentioned drugs; it is seen justifying the novelty of the compositions where Hupu gum is incorporated as an excipient in controlled drug delivery system, which will drastically reduce the prices of the commercially available formulations. Process for preparation of pharamaceutical composition and controlled release drug delivery systems containing a novel polysaccharides excipient, Hupu gum is claimed by us as being highly efficient and economic.
Detailed description:
Hupu gum was evaluated for its physico-chemical and micromeritic properties and microbial load of the gum.
Preparation of the Hupu gum:
The gum is available as transparent pale yellow colored lumps having characteristic slight
salty taste. These lumps were crushed to powder using a laboratory scale grinder. The
resulting powder is passed through mesh # 100. The powder collected was used for further
studies.
Characterization of Hupu gum:
Flow properties of powder are very important in the pre-formulation studies for the preparation of tablets and capsules. The flow properties of the powders can be predicted from the values of bulk density, bulkiness, tapped density, angle of repose, compressibility index and Hausner index.
Hupu gum was evaluated for its pH, swelling index, water absorption properties and visco elastic properties. The results are shown in Table 1. It was subjected to thermal analysis by DSC.
Microbial load of the Hupu gum:
Hupu gum was tested for microbial burden immediately after its receipt and results are
showed in the Table 2.

The results of true density, bulk density, bulkiness, angle of repose, compressibility index, Hausner index, pH and viscosity of HG are given in Table 1.
The values of tapped density, bulk density, compressibility index and angle of repose exhibited by Hupu gum clearly indicated that Hupu gum had good flow properties and was suitable for direct compression. The pH of 1% w/v solution of Hupu gum was found to be 4.9 indicating that gum is slightly acidic in nature. High value of swelling index indicated the high swelling ability of the carrier. Visco elastic properties of Hupu gum revealed that it followed pseudo plasticity.
DSC thermogram of Hupu gum exhibited a broad endothermic peak at 98.9°C, owing to its amorphous character.

Preparation of Hupu gum matrix tablets of Rifampicin and their evaluation:
Rifampicin, a semi synthetic hydrazine derivative of rifamycin B, one of the most potent and powerful mycobactericidal drugs is used mainly in intermittent therapy, both in tuberculosis and leprosy, because of its high cost and adverse side effects. Chemically it is designated as (12Z, 14E, 24EH2S, 16S, 17S, 18R, 19R, 20R, 21S, 22R, 23S)-l,2-dihydro-5, 6, 9, 17, 19 -pentahydroxy - 23 - methoxy - 2,4, 12, 16, 18, 20, 22-heptamethyl-8-(4-methyl piperazin-1-yliminomethyl)-l,l l-dioxo-2,7(epoxy-pentadeca-l,l l,13-trienimino)aphtha[2,l-b] furan-21-yl acetate, which is produced by a strain of Streptomyces mediterranei. Drug passed through mesh # lOOwas used in the present study.
Methods of analysis used in present investigation
The methods available for the estimation of Rifampicin are briefly reviewed here. Spectrophotometric method based on the measurement of absorbance of solution of Rifampicin in pH 7.4 phosphate buffer at 475 nm was official in LP., B.P. and U.S.P. The method reported in the Indian Pharmacopoeia 1996 was used in the present study with a minor modification. Method described in the LP. used pH 7.4 phosphate buffer for the preparation of standard solutions whereas in the present study 0.02% w/v of ascorbic acid was also added to prevent the decomposition of soluble Rifampicin.

PREPARATION OF HUPU GUM MATRIX TABLETS
Direct compression method:
The drug and the Hupu gum sufficient for a batch of 100 tablets, as shown in Table 3, were passed through mesh 100, mixed thoroughly with aerosil and passed through mesh 40 to ensure complete mixing. Then the blend was lubricated with magnesium stearate. Tablets containing Rifampicin equivalent to 300mg were compressed using 13 mm flat round punches on 16 station Cadmach Rotary Compression Machine. Compression force of the machine was adjusted to obtain hardness in the range of 5-6 Kg/cm . Aerosil was used in the formulations to enhance the flow properties of final blend.

Estimation of drug content:
From each batch of prepared tablets, five tablets were randomly collected and powdered. A quantity of powder equivalent to 100 mg was transferred into a 100 ml volumetric flask, sufficient amount of methanol was added to produce 100 ml. Shaken for 20 minutes and filtered. Diluted 2 ml of the filtrate to 100 ml with pH 7.4 phosphate buffer containing ascorbic acid and assayed for the drug content by the method described earlier.
Differential Scanning Calorimetry (DSC):
Differential Scanning Calorimetry of Rifampicin and Rifampicin-Hupu gum compressed tablet was performed in the temperature range of 30°C to 300°C using Shimadzu DSC-50 thermal analyzer under static air atmosphere. Samples were placed in an aluminium pan and heated at a rate of 10°C/minute with an empty pan as reference.

Infrared spectroscopy (IR):
Infrared spectra of the pure Rifampicin and Rifampicin contained Hupu gum matrix were determined from mineral acid mull using PERKIN-ELMER 841 IR spectrophotometer. The scanning range used was 4000 to 600 cm"^
In vitro dissolution studies:
Dissolution test was carried out using USP XXIV type-I (Basket) dissolution rate test apparatus (model DISSO 2000, M/s, Labindia). The stirring rate was 100 rpm. The pH 7.4 phosphate buffer containing ascorbic acid (200 )u,g/ml) was used as dissolution medium (900 ml) and was maintained at 37 ± 0.5°C. Samples of 5 ml were withdrawn at predetermined time intervals with syringe fitted with a filter. The collected samples were diluted suitably, wherever necessary and were analyzed for the Rifampicin content by spectrophotometric method at 475 nm. The volume withdrawn at each time interval was replaced with fresh quantity of 5 ml of dissolution medium. Each dissolution study was performed for three times and mean values taken were reported.
At the end of 12 hrs of dissolution testing, the tablet remains were collected from the basket by thorough washing with methanol into a 100ml volumetric flask for estimation of the remaining drug content. The volume was made up to 100ml with methanol. Suitable dilutions were made with pH 7.4 phosphate buffer and remaining drug content was assayed. This is to make sure that the amount of drug remaining adds to the drug release to give total mass balance of drug content.
Other tests like weight variation, hardness, friability etc. were carried out and the resuhs are found to be satisfactory and with in the limits.
Effect of Channeling Agents on Rifampicin Release Kinetics:
Various channeling agents like Mannitol (RIF-T300-F007A-C), Sorbitol (RIF-T300-F008A-C), Lactose (RIF-T300-F009A-C), Dextrose (RIF-T300-F010A-C) were studied on the release pattern of Rifampicin matrix tablets in different concentrations like 5%, 10%, 15%. The Formulation RIF-T300-F004 was selected and the various concentrations of channeling agents were added and evaluated for their in vitro dissolution release pattern and subjected to assay, IR, DSC studies.

The in vitro dissolution studies of the prepared tablets revealed that the Hupu gum behaved differently depending on the proportions used in the tablet preparation as shown in Fig.l. Generally, in hydrophilic matrix controlled release tablets, initial burst release is observed due to two factors. If the surface area of the polymer is not large enough to cover the drug particle at the surface of the matrix, there is a great chance of burst effect in drug release. Secondly, if the polymer does not hydrate quickly, the surface barrier cannot be formed immediately, which may cause a large portion of drug to be released during the initial phase of release profile. Thus, the surface area as well as the hydration rate of the polymer can play an important role in drug release from matrix tablets, especially at the beginning of the release profile. That quick hydration and subsequent gel formation are foremost and important properties of an excipient for it to be used for controlled release formulation. In Hupu gum matrix tablets, there was no initial bursting effect due to its quick hydration and immediate formation of gel structure around the tablet.
The influence of compression force on release kinetics is not very important for hydrophilic matrices, however, this fact is only observed from compression force adequate to prevent the partial or total matrix disintegration. In the present work the compression force of the tablet machine was so adjusted that made it possible to obtain tablets whose hardness level was between 5-6 kg/cm . The weight variations of the tablets were within the Pharmacopoeial limits (not more than two of the 20 tablets differ from the average weight by more than 5% and no tablet differs by more than 10%).
The release rate constants revealed that the release rate increased as the proportion of Hupu gum decreased and followed first order release kinetics. In order to establish the mechanism of drug release, the experimental data were fitted to the exponential equation (MJ/MQ^ =
Kt"). The linear correlation coefficients of the slopes and slope values shown indicated that the release kinetics confirm predominantly to non- fickian diffusion (i.e. square root of time profile). This classical Higuchi type of release mechanism can be explained as a result of the rapid hydration of the polymer molecules on the surface of the tablets, which results in a gel or a highly viscous solution surrounding the matrix that restricts water penetration into the center. The net result is a reduction of the rate of drug release as a function of time. This was confirmed by the linearity of the plot obtained when cumulative amount of drug released was plotted as a function of square root of time (t'^')-

The DSC thermograms revealed that there is no interaction or complexation occurred between Rifampicin and Hupu gum during the manufacturing process.
The channeling agents when in contact with the dissolution fluid immediately dissolves and creates channels in the matrix tablets and there by enhanced the release of Rifampicin. The channeling agents mannitol, sorbitol, lactose, dextrose significantly enhanced the release of Rifampicin from the selected formulation RIF-T300-F004. No significant difference in release rate was observed up to 5% concentration of channeling agents. At 10% concentration Sorbitol and Dextrose increased the Rifampicin release whereas with Mannitol and lactose no significant increment in Rifampicin release rate. At 15% concentration significant enhancement in release of Rifampicin was observed. Beyond the concentration 15% of channeling agents, the hardness of the tablets was reduced and prone for higher friability values. Among the studied channeling agents Sorbitol was found to increase the release of Rifampicin to 88% from 28% at the end of 12hrs. Release rate followed first order kinetics and by non-fickian diffusion mechanism. The effect of channeling agent was in the order of Sorbitol > Dextrose > Lactose > Mannitol (Fig.2-5).
Preparation of Hupu Gum Matrix Tablets of Diclofenac Sodium and their Evaluation:
In the next phase Hupu gum matrix tablets were prepared with Diclofenac sodium. Diclofenac sodium (DS), a substituted phenyl-acetic acid derivative, designated chemically as 2-[(2,6-dichlorophenyl)-amino]-benzene acetic acid mono sodium salt. It is a nonsteroidal anti-inflammatory drug (NSAID) widely used in the management of many inflammatory conditions. In addition to its anti-inflammatory effect, DS has analgesic and anti-pyretic action. It is official in Indian Pharmacopoeia (IP), British Pharmacopoeia (BP) and United States Pharmacopoeia (USP). Diclofenac sodium is a white or slightly yellowish, slightly hygroscopic, crystalline powder. It is acidic in nature, freely soluble in methanol, soluble in ethanol and is sparingly soluble in water. The reported solubility in water is 36 mg/ml^
Method of Analysis Used in Present Investigation
A spectrophotometric method based on the measurement of absorbance at 275 nm in phosphate buffer (pH 7.4) was used in the present study for the estimation of Diclofenac sodium from the samples.

Preparation ofHupu Gum Matrix Tablets of Diclofenac Sodium
Wet granulation method
The drug and different proportions of Hupu gum as shown in Table 4, sufficient for a batch of 100 tablets were passed through a 100 No. Sieve and thoroughly mixed to ensure complete mixing and granulated with 70% Isopropyl alcohol. The wet mass was dried in a hot air oven at not more that 50°C until LOD (Loss on drying) reaches with in 2-3%. Dried granules were lubricated with mesh 40 passed Mg stearate and stored in a tightly packed container. Tablets containing Diclofenac sodium equivalent to lOOmg were compressed using 9 mm, slightly concave round punches on 16 stations Cadmach rotary compression machine. Compression force of the machine was adjusted to obtain hardness in the range of 5-6 Kg/cml

In vitro dissolution studies:
Dissolution test was carried out using USP XXIV type-I (Basket) dissolution rate test apparatus (model DISSO 2000, M/S Labindia) at 100 rpm. The pH 7.4 phosphate buffer was used as dissolution medium (900 ml) and was maintained at 37 ± 0.5^C. Samples of 5 ml were withdrawn at predetermined time and were analyzed for the Diclofenac sodium content by spectrophotometric method at 275 nm. Each dissolution study was performed for three times and mean values taken were reported.
Preparation of Hupu Gum Matrix Tablets of Diltiazem Hydrochloride and their Evaluation
Hupu gum matrix tablets were prepared with Diltiazem Hydrochloride. Diltiazem hydrochloride is (+)-5-[2-(dimethylamino)ethyl]-cis, 2,3dihydro- 3-hydroxy-2-(p"

methoxyphenyl)"l,5-benzo-thia2epin-4(5H)-one acetate monohydrochloride. It is an important coronary vasodilator drug of the calcium channel-blocker, used in the therapy of heart disease and hypertension. The compound also exhibits weak negative inotropic and chronotropic actions as well as a weak hypotensive activity
Method of Analysis Used in Present Investigation
A spectrophotometric method based on the measurement of absorbance at 238 nm in
Distilled water was used in the present study for the estimation of Diltiazem Hcl from the
samples.
Preparation ofHupu Gum Matrix Tablets of Diltiazem hydrochloride
Wet granulation method
The drug and different proportions of Hupu gum shown in Table 5, sufficient for a batch of 100 tablets were passed through a 100 No. Sieve and thoroughly mixed to ensure complete mixing and granulated with 70% Isopropyl alcohol. The wet mass was dried in a hot air oven at not more that SOT until LOD (Loss on drying) reaches with in 2-3%. Dried granules were lubricated and stored in a tightly packed container. Tablets containing Diltiazem hydrochloride equivalent to 90mg were compressed using 9 mm, slightly concave round punches on 16 stations Cadmach rotary compression machine. Compression force of the machine was adjusted to obtain hardness in the range of 5-6 kg /Cm^.

In vitro dissolution studies:
Dissolution test was carried out using USP XXIV type-I (Basket) dissolution rate test apparatus (model DISSO 2000, M/S Labindia) at 100 rpm. Distilled water used as dissolution medium (900 ml) and was maintained at 37 ± 0.5°C. Samples of 5 ml were withdrawn at predetermined time intervals and were analyzed for the Diltiazem HCl content

by spectrophotometric method at 238nm. Each dissolution study was performed for three times and mean values taken were reported.
Dissolution profiles of prepared Diclofenac sodium formulations were showed in the Fig.6 where as dissolution profile of Diltiazem HCl were showed in Fig.7. Release kinetics of Diclofenac sodium and Diltiazem HCl were followed first order kinetics and the release kinetics conforms predominantly to non- fickian diffusion (i.e. square root of time profile). This classical Higuchi type of release mechanism can be explained as a result of the rapid hydration of the polymer molecules on the surface of the tablets, which results in a gel or a highly viscous solution surrounding the matrix that restricts water penetration into the center. The net result is a reduction of the rate of drug release as a function of time.
Detailed Description of Drawings:
Fig.l illustrates describes the dissolution profiles of Rifampicin from Hupu gum matrix formulations. In Fig.l, numbers 1-6 represents different formulation codes containing different Hupu gum concentrations which are RIF-T300- FOOl, RIF-T300-F002, RIF-3000-F003, RIF-T300-F004, RIF-300-F005 and RIF-300-F006 respectively. 7 represents X- axis which denotes time in hours and 8 represents Y-axis which denotes cumulative percent drug released. Fig.l reveals that Hupu gum behaved differently depending on the proportions used in the formulations.
Fig.2 describes the effect of channeling agent, mannitol on the formulation code of Rifampicin, RIF- T300-F004. In Fig .2, numbers 9-12 represents different formulation codes containing mannitol in different concentrations such as 0, 5, 10, and 15%, RIF- T300-F004, RIF.T300-F007A, RIF-T300-F007B, RIF-300-F007C respectively. From the Fig.2 it is come to know that 15% concentration of the channeling agent in the formulation has increased the drug release. 13 denotes X- axis which is time in hours, and 14 denotes Y- axis which is percent release of the drug.
Fig.3 describes the effect of channeling agent sorbitol in the formulafion code of Rifampicin RIF-300-F004, In Fig .3, numbers 15-18 represents different formulation codes containing sorbitol in different concentrations, RIF- T300-F004, RIF-T300-F008A, RIF-T300-F008B, RIF-300-F008C respectively. Fig.3 shows that 15% concentration of the channeling agent in

the formulation has increased the drug release. 19 denotes X- axis which is time in hours, and 20 denotes Y- axis which is percent release of the drug.
Fig.4 describes the effect of channeling agent lactose in the formulation code of Rifampicin RIF-300-F004. In Fig .4, numbers 21-24 represents different formulation codes containing lactose in different concentrations, RIF- T300-F004, RIF-T300-F009A, RIF-T300-F009B, RIF-300-F009C respectively. Fig.4 shows that 15% concentration of the channeling agent in the formulation has increased the drug release. 25 denotes X- axis which is time in hours, and 26 denotes Y- axis which is percent release of the drug.
Fig.5 describes the effect of channeling agent dextrose in the formulation code of Rifampicin RIF-300-F004, In Fig .5, numbers 27-30 represents different formulation codes containing dextrose in different concentrations, RIF- T300-F004, RIF-T300-F0010A, RIF-T300-FOOIOB, RIF-300-F0010C respectively. Fig.5 illustrates that it is come to know that 15% concentration of the channeling agent in the formulation has increased the drug release. 31 denotes X- axis which is time in hours, and 32 denotes Y- axis which is percent release of the drug.
Fig.6 describes the dissolution profiles of Diclofenac sodium from Hupu gum matrix formulations. In Fig.6, numbers 33-36 represents different formulation codes containing different Hupu gum concentrations, DFS-T-100-FOOl, DFS-T100-F002, DFS-T100-F003, DFS-T100-F004, respectively. 37 denote X- axis which is time in hours and 38 denotes Y-axis which is cumulative percent drug released. Fig.6 reveals that Hupu gum behaved differently depending on the proportions used in the formulations. Release kinetics showed first order kinetics and confirms predominantly to non- fickian diffusion.
Fig.7 describes the dissolution profiles of Diltiazem hydrochloride from Hupu gum matrix formulations. In Fig.7, numbers 39-42 represents different formulation codes containing different Hupu gum concentrations, DIL-T-90-F001, DIL-T90-F002, DIL-T90-F003, DIL-T90-F004, respectively. 39 denotes X- axis which is time in hours and 40 denotes Y-axis which is cumulative percent drug released. Fig.7 reveals that Hupu gum behaved differently depending on the proportions used in the formulations. Release kinetics showed first order kinetics and confirms predominantly to non- fickian diffusion.

While the present invention is described above in connection with preferred or illustrative embodiments, these embodiments are not intended to be exhaustive or limiting of the invention. Rather, the invention is intended to cover all alternatives, modifications and equivalents included within its scope.
Form the above studies, it can be concluded that Hupu gum could be efficiently used as sustained release excipient in wet granulation as well as direct compression techniques for the various classes of drugs like freely soluble, partially soluble and slightly soluble drugs in the design of controlled drug delivery systems.

I claim,
1. The process for preparation of novel pharmaceutical compositions for controlled
release drug delivery systems comprising novel poly saccharide excipient (Hupu
gum) and an active agent, wherein said process comprises;
Mixing of drug and Hupu gum; passing through 100 mesh; mixing thoroughly with aerosil; passing through 40 mesh to ensure uniform mixing; lubricating the blend with magnesium stearate and compressing into tablets.
2. The process as claimed in claim 1, wherein the said drug is selected from partially soluble drug such as Rifampicin.
3. The process as claimed in claim 1, wherein the said aerocil is used to increase the flow properties of the blend.

4. The process as claimed in claim 1, wherein the said process is direct compression.
5. The process as claimed in claim 1, wherein the said process is used to prepare controlled release drug delivery systems by using novel excipient Hupu gum.
6. The process as claimed in claim 1, wherein the said process is used to prepare sustained release drug delivery systems by using novel excipient Hupu gum
7. The process as claimed in claim 1, wherein the said process is used to prepare modified release drug delivery systems by using novel excipient Hupu gum.
8. The process as claimed in claim 1, wherein the said process is used to prepare delayed release drug delivery systems by using novel excipient Hupu gum.
9. The process for preparation of novel pharmaceutical compositions for controlled release drug delivery systems comprising as an excipient (Hupu gum) and an active agent, wherein the said process comprises,

Mixing of drug and Hupu gum; passing through 100 mesh; mixing thoroughly; granulating with 70%isopropyl alcohol; drying the wet mass in hot air oven at not more than that 50°C until LOD reaches within 2-3%;lubricating the dried granules with 40 mesh magnesium stearate and compressing said lubricate into tablet with tablet punches.
10. The process as claimed in claim 9, wherein said drug is selected from freely soluble drugs like Diltiazem hydrochloride and sparingly soluble drugs like Diclofenac sodium.
11. The process as claimed in claim 9, wherein said drug is Diltiazem hydrochloride.
12. The process as claimed in claim 9, wherein said drug is Diclofenac sodium.
13. The process as claimed in claim 9, wherein said process is wet granulation.
14. The process as claimed in claim 9, wherein said process is used to prepare controlled release drug delivery systems by using novel excipient Hupu gum.
15. The process as claimed in claim 9, wherein said process is used to prepare sustained release drug delivery systems by using novel excipient Hupu gum
16. The process as claimed in claim 9, wherein said process is used to prepare modified release drug delivery systems by using novel excipient Hupu gum.
17. The process as claimed in claim 9, wherein said process is used to prepare delayed release drug delivery systems by using novel excipient Hupu gum.
18. The process for preparation of novel pharmaceutical composition for controlled release drug delivery system as claimed in claim 1 and 9, wherein the said Hupu gum is prepared by a method comprising;
crushing the pale yellow colored lumps into powder using a laboratory scale grinder; passing through 100 mesh and collecting the powder.

19. The process for preparation of novel pharmaceutical composition and controlled
release drug delivery systems wherein, that there is no interaction or complexation
occurred between Rifampicin and Hupu gum during the manufacturing process.
20. The process for preparation of novel pharmaceutical composition and controlled
release drug delivery systems comprising a novel excipient Hupu gum as
substantially described herein with reference to the foregoing examples 1 to3.

Documents:

953-che-2003-abstract.pdf

953-che-2003-claims.pdf

953-che-2003-correspondnece-others.pdf

953-che-2003-correspondnece-po.pdf

953-che-2003-description(complete).pdf

953-che-2003-description(provisional).pdf

953-che-2003-drawings.pdf

953-che-2003-form 1.pdf

953-che-2003-form 18.pdf

953-che-2003-form 3.pdf

953-che-2003-form 5.pdf

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Patent Number

229191

Indian Patent Application Number

953/CHE/2003

PG Journal Number

12/2009

Publication Date

20-Mar-2009

Grant Date

13-Feb-2009

Date of Filing

21-Nov-2003

Name of Patentee

KOLAPALLI VENKATA RAMANA MURTHY

Applicant Address

DEPARTMENT OF PHARMACEUTICAL SCIENCES, ANDHRA UNIVERSITY, VISAKHAPATNAM - 530 003,

Inventors:

#	Inventor's Name	Inventor's Address
1	KOLAPALLI VENKATA RAMANA MURTHY	DEPARTMENT OF PHARMACEUTICAL SCIENCES, ANDHRA UNIVERSITY, VISAKHAPATNAM - 30 003,
2	AVVARU SESHASAYANA	DEPARTMENT OF PHARMACEUTICAL SCIENCES, ANDHRA UNIVERSITY, VISAKHAPATNAM - 530 003,

PCT International Classification Number

A61K35/78

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA