Title of Invention

A TRANSMUCOSAL DRUG DELIVERY SYSTEM AND ITS PREPARATION FOR BENZIMIDAZOLE CLASS OF PROTON PUMP INHIBITORS

Abstract

The novel transmucosal dosage form of this invention relates to benzimidazole class of proton pump inhibitors and their precursors, derivatives or salts for the delivery of the drugs through the oral mucosa. The novel transmucosal dosage forms do not require enteric coating, or any other coating or excess sodium ions commonly employed for this class of drugs. Commonly used site of absorption for this invention relates to sublingual, gingival or other sites on the oral mucosa.

Full Text

FORM - 2 THE PATENTS ACT, 1970 (39 OF 1970) COMPLETE SPECIFICATION [SECTION 10; RULE 13] 1. A TRANSMUCOSAL DRUG DELIVERY SYSTEM AND ITS PREPARATION FOR BENZIMIDAZOLE CLASS OF PROTON PUMP INHIBITORS. 2. (a) Astron Research Pvt. Ltd. (b) 2nd Floor Premier House 1, Bodakdev, Ahmedabad-380054. Gujarat State, India. (c) INDIA. The following specification particularly describes and ascertains the nature of the invention and the manner in which it is to be performed. 3 1 The present invention relates to a transmucosal drug delivery system and its preparation for Benzimidazole class of proton pump inhibitors. In the present invention, transmucosal drug delivery system is prepared using uncoated Benzimidazole proton pump inhibitors. The said transmucosal system or tablet is prepared using proton pump inhibitors of Benzimidazole class. The objective of the invention is to absorb the oral transmucosal dosage form in mouth cavity. The routes of administration of the said transmucosal drug are sublingual buccal, gingival. The administration of dosage form containing Benzimidazole class of proton pump inhibitors, suppresses gastric acid secretion at the secretory surface of gastric parietal cells. Background of the inventions: Benzimidazole class of PPI, that inhibits gastric acid secretion are typically available as enteric coated tablets, pellets or granules or orally disintegrating tablet consisting of enteric coated drug. The use of enteric coating of the drug is essential as this class of drugs is prone to acid degradation. Manufacturing process for enteric coated pellets or tablets is cumbersome process. Also, the absorption and thereby onset of action of the drug is delayed. There is also food effect in the 2 absorption of the drug. The drugs also undergo extensive hepatic first pass metabolism. For acute and chronic cases of gastric ulcer, duodenal ulcers, GERD, severe erosive oesphagitis and other pathological hypersecretory conditions such as Zollinger Ellison syndrome, a fast acting dosage form is the purpose of the invention. US patent 6,498,171 claims a pharmaceutical composition of hydroxyomeprazole and their salts in tablet or capsule oral dosage form for the treatment of ulcers of stomach, duodenum and esophagus, gastroesophageal reflux disease, Zollinger-Ellison Syndrome, psoriasis. The active pharmaceutical substance hydroxyomeprazole or a pharmaceutically acceptable salt thereof, is preferably used about 100-500 mg of the total weight of the Tablet or capsule. Due to acid instability of hydroxyomeprazole, sustain release enteric coated tablet or capsule is prepared. US patent 6,328,993 claims for a novel oral administration form for plurality of acid-labile uncoated individual active compound units. Where in the active compound is surrounded by a mixture of at least one sterol and at least one polymer, by at least one fatty alcohol or by a mixture of at least one fatty alcohol and at least one polymer and/or at least one sterol. Acid labile proton pump inhibitors of Benzimidazole are active compound units used in the invention. 3 US patent 6,365,184 describes the oral, multiple unit tableted dosage form comprising an anti-ulcer drug, preferably an acid susceptible proton pump inhibitor in the form of individually enteric coating layered units, together with one or more NSAIDs (nonsteroidal antiinflamatory drugs) and tablet excipients. / US patent 6,296,876 claims on an enteric coated oral dosage form of a selected acid labile compound, in particular proton pump inhibitor compounds which decrease production of acid in the gut. The novel pharmaceutical composition comprises about 1 to 75% by weight an acid labile compound, acid sequestering compound(s), upto about 5% by weight disintegrant and at least one coating layer. US patent 6,489,346 covers substituted Benzimidazole dosage forms and methods of using same. Wherein solid pharmaceutical composition, a dosage form is prepared including non-enteric coated (uncoated) proton pump inhibitor approximately 5mg to 300 mg and with the use of excess of buffering agents in the range of approximately 0.1 m.Eq to 2.5 m.Eq per mg of PPI. Wherein the dosage form is selected from the group consisting of suspension tablet, chewable tablet, effervescent powder and effervescent tablet. US patent 6,303,147 describe on a bioadhesive pharmaceutical composition comprising a pharmaceutically effective amount of an active ingredient, from 80% to 98.8% w/w pre-gelatinzed starch, from 1% to 10% 4 w/w of a hydrophilic matrix forming polymer, characterized in that the composition further comprises from 0.2% to 5% w/w of alkali C16-23 alkyl fumarate as a lubricant. US patent 5,723,114 describes a method for enhancing permeation of a topically administered therapeutic or prophylactic agent in a host in need of the cutaneous or transdermal administration of a therapeutic or prophylactic agent. Wherein the penetration enhancing compound is selected from the group consisting of lasalocid, nigericin,valinomycin, chloroquine, gramicidin D, salinomycin, N-ethylmaleimide, N,N-dicyclohexyl carbodiimine and bafilomycin A1 or B1. US patent Application 20030166553 describes a composition for preventing and treating digestive organs diseases. The composition is prepared using among other potential pharmaceutical agents and dosage forms, proton pump inhibitors and transmucosal drug. Generally enteric coated tablet of proton pump inhibitors (PPI) of Benzimidazole class are dissolve in Gl tract below the stomach, after it passed through the stomach without getting degraded. So the onset of action is delayed. To overcome the drawback of enteric coated tablet of PPI of Benzimidazole class, uncoated transmucosal drug delivery system for PPIs of Benzimidazole class is prepared. 5 Disclosure of the Invention: The objective of the present invention is to formulate uncoated transmucosal drug delivery system (tablet) of stable dosage form and fast dissolution of dosage form and absorption in oral cavity. Its flavoured taste gives better patient compliance. Proton Pump Inhibitors of Benzimidazole class are Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole and similar compounds such as salts, derivatives and isomers used for the treatment of Gastro Endothelial Related Diseases (GERD) and other pathological hyper secretory conditions. According to the present invention, a method of producing mucosal delivery drugs is outlined below wherein the drug Lansoprazole is either mixed in directly compressible ingredients or granules of the same are manufactured using wet granulation or dry granulation method. Lactose, MCC, mannitol, sodium bicarbonate, Di-sodium hydrogen orthophosphate, magnesium carbonate, sucrose or glucose are used as diluents and directly compressed in tablet form; lysine or glycine are used as stabilizer in preparation of drug delivery system. Sodium hydroxide is also used as stabilizer of the drug. Sodium lauryl sulphate, croscarmellose sodium, crospovidone, SSG, indion (resin) are used to achieve appropriate disintegration. Sodium stearyl fumarate is used as lubricant. Cellulose ethers or alginates are used as mucoadhesive polymer. The present invention relates to use of PPI"s in the uncoated form, which is administered in oral cavity e.g. sublingual, buccal and gingival. 6 The invention also describes the dosage form which eliminates the destabilizing effect of PPI"s by gastric juice and avoids extensive hepatic metabolism commonly encounters with this class of drugs. Use of oral drug delivery system (DDS) will also help in reducing the onset of action and reduce dosage requirement. Incventive composition comprises Proton Pump Inhibitors (PPI) as active ingredients. Lansoprazole, Omeprazole, Pantoprazole, Esomeprazole, Pariprazoie, Lamiprazole, Rabeprazole and their salts, derivatives and isomers are Proton Pump Inhibitors (PPI) of Benzimidazole class. Inventive composition is oral transmucosal drug delivery system and prepared by using either dry granulation or wet granulation or direct compression method. These PPI are degraded in aqueous solution and the rate of degradation in aqueous solution increases with respect to decrease in pH of the aq. Solution. The pH of oral saliva is about 6.5 and PPI"s are stable enough in this pH to allow them to be absorbed whereas these are quite unstable and degrade in low acidic pH of the stomach. Once the tablet (drug delivery system) absorbed through oral mucosal layer, drug is available to various tissue through blood stream including parietal cells to elicit the desired pharmacological actions. The said transmucosal tablet is administered by keeping the dosage form under the tongue or under the cheek (gingival), or between the cheek and gum to aid absorption through oral mucosal without swallowing. 7 Examples : Example l:Preparation of transmucosal Tablets of Lansoprazole using Direct Compression Method:- Sr. No. Ingredients Example 1 % w/w Example 2 " % w/w 1 Lansoprazole 24 19.7 2 MCC PH 102 40 - 3 Mannitol (Free Flow) - 63.2 4 Sodium Bicarbonate 2.4 - 5 Di Sodium Hydrogen Ortho Phosphate - 2.6 6 Magnesium Carbonate 24 - 7 Colloid Anhydrous Silica 0.8 1.32 8 PVP K30 - 1.32 9 Sodium Stearyl Fumarate 1.6 1.32 10 Sodium Starch Glycolate 4.8 - 11 Crospovidone - 7.9 11 Aspartame 2.4 1.32 13 Flavour - 1.32 Hardness 7 to 9 kp 5 to 6 kp Disintegration Time 20 seconds 30 seconds Manufacturing Process Lansoprazole was mixed with Sodium Bicarbonate or Di Sodium Hydrogen Orthophosphate. The blend was further mixed with other ingredients and was compressed into tablets. 9 Example 2:Preparation of trans mucosa l Tablets of Lansoprazole using Dry Granulation Method:- Sr. No. Ingredients Example 3A % w/w Example 3B % w/w Example 3C % w/w Example 4 % w/w 1 Lansoprazole 21.6 20.1 14.4 22.2 2 MCC PH 102 - - 23.9 59.2 3 Beta Hydroxy Propyl Cyclodextrin 69.8 65.1 46.4 4 Sodium Bicarbonate 2.2 2.0 1.4 - 5 Di Sodium Hydrogen Ortho Phosphate 3.0 6 Colloid Anhydrous Silica 1.4 1.4 1.0 1.5 7 Sodium Stearyl Fumarate 1.4 1.4 1.0 1.5 8 Croscarmellose Sodium - 6.7 9.6 8.9 9 Aspartame 2.2 2.0 1.4 2.2 10 Flavour 1.4 1.3 1.0 1.5 Hardness 8 to 10 3 to 5 2 to3 3.5 to 4.5 ! Disintegration Time 12 min 9 min 6.5 min 15 second Man Hyd ufacturing Process ;Lansoprazole was rogen Orthophosphate. The b was mixe lend was furtl i with Sodium ler mixed with Bicarbonate or Di Sodium other ingredients and was Example 3:Preparation of transmucosal Tablets of Lansoprazole using Wet Granulation Method:- Sr. No. Ingredients Example 5 % w/w Example 6 % w/w Example 7 % w/w 1 Lansoprazole 21.3 21.3 24 2 Lactose Monohydrate 35.5 35.5 3 MCC PH 102 - - 40 4 Mannitol 7.0 7.0 5 Sodium Bicarbonate 2.1 2.1 2.4 6 Magnesium Carbonate 21.3 21.3 24 7 Starch 7.0 7.0 8 Colloid Anhydrous Silica 0.8 9 Sodium Stearyl Fumarate 1.42 1.42 1.6 10 Sodium Starch Glycolate 4.3 11 Croscarmellose Sodium - 4.3 4.8 Aspartame - - 2.4 Hardness 7 to 10 kp 7 to 10 kp 4 to 5 kp ! Disintegration Time 4 minutes 3.5 minute 20 seconds j Manufacturing Process :Lansoprazole was mixed with Sodium Bicarbonate, Magnesium Carbonate, Lactose Monohydrate, Mannitol and MCC PH 102. The blend was granulated with Starch paste or Purified water. The wet granules were dried in Tray dryer. The dried granules were mixed with j lubricants and compressed into the tablets. 10 Example 4:Preparation of Transmucosal Tablets of Lansoprazole using Wet Granulation Method:- Sr. No. Ingredients Example 8 % w/w Example 9 % w/w Example 10 % w/w 1 Lansoprazole 30 30 23.6 2 Lactose Monohydrate 15 15 - 3 MCC PH 102 15 15 39.4 4 Mannitol 10 10 - 5 Sodium Bicarbonate 3 3 2.4 6 Magnesium Carbonate 15 15 23.6 7 Colloid Anhydrous Silica 1 1 0.8 8 Sodium Stearyl Fumarate 2 2 1.6 9 Sodium Starch Glycolate 6 4.7 10 Croscarmellose Sodium - 6 - 11 Aspartame 3 3 2.4 12 Flavour - 1.6 | Hardness 3 to 5 kp 3 to 5 kp 3 to 6 kp Disintegration Time 30 seconds 30 seconds 30 seconds I Manufacturing Process lansoprazole was mixed with Sodium Bicarbonate, I Magnesium Carbonate, Lactose Monohydrate, Mannitol and MCC PH 102. The blend was granulated with Purified water. The wet granules were dried in Tray dryer. The dried granules were mixed with lubricants and ; compressed into the tablets. I 11 Example 5:Preparation of Transmucosal Tablets of Lansoprazole using Wet Granulation Method:- Sr. No. Ingredients Example 11 % w/w Example 12 % w/w Example 13 , % W/W i 1 Lansoprazole 15.3 24.6 20 | 2 Mannitol 71.5 52.5 64 3 Sucrose 2.0 - 4 Di Sodium Hydrogen Orthophosphate 2.0 3.3 2.7 I 5 PVP K30 2.0 1.6 1.3 ! 6 Sodium Stearyl Fumarate 1.0 1.6 1.3 i 7 Crospovidone 6.1 9.8 8 J 8 Aspartame - 1.6 1.3 9 Flavour - 1.6 1.3 Hardness 2 to 3 kp 1.5 to 2.5 kp 2to3kp Man Hyd gran Spir gran Disintegration Time ufacturing Process :Lar rogen Orthophosphate, ulated with PVP K30 soli t in ratio of 1:1. The wet ules were mixed with lubr 15 seconds isoprazole wa Mannitol and ition in Purifiec granules were icants and com] 30 to 40 30 to 40 i seconds seconds Example 6:Preparation of Transmucosai Tablets of Lansoprazole using Wet Granulation Method:- Sr. No. Ingredients Example 14 % w/w Example 15 % w/w Example 16 % w/w 1 Lansoprazole 18.4 23 23 2 Mannitol 58.9 49.8 49.8 3 Di Sodium Hydrogen Orthophosphate 2.5 3.0 4 Sodium Hydroxide - - 3.0 5 Hydroxy Propyl Cellulose 7.7 7.7 6 PVP K30 1.2 - 7 Sodium Stearyl Fumarate 1.2 1.5 1.5 8 Talc - 4.6 4.6 9 Crospovidone - 9.2 9.2 10 Indion 234 15.3 - - 11 Aspartame 1.2 0.8 0.8 12 Flavour 1.2 0.4 0.4 Hardness 2 to 3 kp 4 to 5 kp 3 to 4 kp Disintegration Time 3 minute 2.5 minute 1.5 to 2 minute Manufacturing Process :Lansoprazole was mixed with Di Sodium Hydrogen Orthophosphate, Mannitol and Hydroxy Propyl Cellulose. The blend was granulated with PVP K30 solution in Purified Water and Special Denatured Spirit in ratio of 1:1 or Sodium Hydroxide solution in Purified Water & Special Denatured Spirit in ration of 1:1. The wet granules were dried in Tray dryer. The dried granules were mixed with lubricants and compressed into the tablets. 13 Example 7:Preparation of Transmucosal Tablets of Lansoprazole using Wet Granulation Method:- Sr. No. Ingredients Example 17 % w/w Example 18 % w/w Example 19 % w/w 1 Lansoprazole 20.8 21.1 19.8 2 Mannitol 66.4 - - 3 Glucose Monohydrate - 61.4 4 MCC PH 101 - 35.2 - 5 Di Sodium Hydrogen Orthophosphate 2.8 - 2.7 6 Sodium Bicarbonate 2.1 - 7 Sodium Lauryl Sulphate - 2 7 Magnesium Carbonate - 21.1 - 8 PVPK30 1.4 9.2 1.3 9 Sodium Stearyl Fumarate 1.4 1.4 1.3 10 Talc 4.2 - 2 11 Sodium Starch Glycolate _ 3.9 - 11 Crospovidone 2.0 4.2 7.9 12 Aspartame 0.7 0.7 1.3 13 Flavour 0.4 0.4 0.3 Hardness 4.5 to 5.5 kp 5 to 6 kp 3.5 to 4.5 kp Disintegration Time 2 minute 1 minute 2.5 minute Man Orth im ufacturing Process :Lansoprazole was mixed with ophosphate or Sodium Bicarbonate, Mannitol, Glucose M Di Sodii onohydrate im Hydrogen and MCC PH Denatured Spirit in ratio of 1:1 The wet granules were dried in Tray dryer. The dried granules were mixed with lubricants and compressed into the tablets. 14 Comparative chart for coated Capsule & uncoated Tablet Formulation: ST. No. Ingredients Capsule Dosage Form Tablet Dosage Form (1st Formulation) Tablet Dosage Form (2nd Formulation) 1 Lansoprazole 20.67 % 20.06 % 20.06 % 2 Non Peril Seeds 27.56 % - - 3 Mannitol 7.20 % 64.21 % - 4 Glucose Monohydrate - - 62.21 % 5 Sodium Hydroxide 0.28 % - - 6 Di Sodium Hydrogen Ortho Phosphate 2.29% 2.68 % 2.68 % 7 Magnesium Carbonate 1.38 % - 8 HPMC 12.40 % - - 8 HPC - 2% - 9 PVPK30 - 1.34% 1.34 % 10 Sodium Lauryl Sulphate - - 2% 11 PEG 6000 1.24 % 12 Sodium Stearyl Fumarate - 1.34 % 1.34% 13 Crospovidone 4.02 % 8.04 % 14 Talc 2.07 % 4.02 % 2% 15 Titanium dioxide 0.69 % - - 15 16 Colloidal Anhydrous silica 0.27 % 17 Flavour " 0.33 % 0.33% COATING FORMULATION 18 HPMC 5.32 % Not Applicable Not Applicable 19 Eudragit L30D55 (Dry Polymer) 10.74 % Not Applicable Not Applicable 20 . Di Ethyl Phthalate 1.61 % Not Applicable Not Applicable 21 Sodium Hydroxide 0.13 % Not Applicable Not Applicable 22 i Tween 80 0.16 % Not Applicable Not Applicable 23 iTalc 4.96 % Not Applicable Not Applicable 24 Titanium Dioxide 0.90 % Not Applicable Not Applicable 25 | Colloid Anhydrous Silica 0.13 % Not Applicable Not Applicable 100.00% 100.00 % 100.00 % The above stated comparative chart involves a process of making the uncoated dosage form of proton pump inhibitors of Benzimidazole class with keeping intact the effectiveness of the drugs e.g. Lansoprazole by eliminating the need of enteric coating. Conventional oral enteric coated capsule or tablet is prepared to delay the release or to protect the acid labile 16 drugs such as PPIs. Absorption of enteric coated tablet/capsule takes place below the stomach in gastro intestinal tract. While in the present invention uncoated transmucosal delivery system prepared, gets release and absorb in oral cavity and therefore does not require coating to protect the drug from acidic environment of stomach. Stability data of Lansoprazole tablet: Lansoprazole Tablet 30 mg LAT1006C App II / 50 RPM / 900ml 6.8 pH Phosphate Buffer ! 40C & 75 % RH ALU- : HDPE ALU pack ALU-ALU HDP E pack ALU-ALU HDPE pack ALU-ALU HDPE pack Initial 1M 1M 2M 2M 3M 3M 6M 6M Dissolution 89 84 83 86 80 83 83 81 84 Assay % 101.5 i 102.2 98.7 98.7 98.6 ! 98.60% j 98.60 % 100.60 % 98.90 % Proton pump inhibitors of Benzimidazole class are unstable in acidic environment and are also labile to heat. Stability data is generated to check under accelerated/stressed condition to prove that the product will be stable during its shelf life up to expiry. The above stability data is generated to check that the said invention of process does not require to protect the drug from acidic environment of stomach and maintain its potency and release of 17 Comparative data of Dissolution of capsule & tablet: Dissolution Conditions Capsule Dosage Form Tablet Dosage Form (Oral Transmucosal Formulation) - USP Apparatus II - 0.1 N HC1 - 500 ml - 100 rpm 60 minutes 0 to 2 % (Specification = NMT 10%) Not Applicable - USP Apparatus II - 6.8 pH Phosphate Buffer - 900 ml - 100 rpm 60 minutes 95 to 99 % (Specification = NLT 80%) i i - USP Apparatus I - 6.8 pH Phosphate Buffer - 500 ml 50 rpm 20 minutes - 90 to 99% (Specification = NLT 80%) 19 The said invention involve a process of making uncoated tablets which are absorbed through oral mucosa and elicits action and does not require to enteric coat to protect the drug from acidic environment of stomach. Presently available capsules or tablets of PPI of Benzimidazole class, involves coating of drug which protects it in stomach but release the drug below the stomach. The conventional enteric coated tablets, therefore require to be evaluated for absorption behavior by dissolution study in stomach for 2 hour (usual duration for stomach emptying/residence time in stomach) followed by phosphate buffer pH 6.8 for 45 minutes. Presented invention involves a transmucosal dosage form, where the absorption behavior can be assessed by doing dissolution study only in phosphate buffer pH 6.8 (approximate pH of oral cavity). Both formulations of Lansoprazole Tablets are studied Following are the results of the study. Pharmacokinetics parameters of Lansoprazole in plasma, following administration of the reference and test formulations 20 c (ug/ml) T max (hr) AUCo.t (Hg.hr/ml) Cmax (Hg/ml Tmax AUCo (hr) (ug.hr/ml) Reference Test 1st Formulation Mean 0.48 1.56 0.88 0.57 0.75 | 0.68 2nd Formulation Mean 0.86 1.50 2.71 0.88 1.06 2.37 The rate maximum and extent of absorption of tablet (tmax) & capsule (Cmax) are compared and tabulated above to show that though tmax is less in test formulation implying faster rate of absorption, extent of absorption is not significantly different. 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, modifications and equivalents included, as defined by appended claims. 21 We claim: 1. A transmucosal drug delivery system and its preparation for Benzimidazole class of proton pump inhibitors (PPIs) for oral mucosal administration comprises, (i) using 2 to 50 % active pharmaceutical ingredient proton pump inhibitor (PPI) of banzimidazole class in uncoated dosage form, in monolithic form of tablet, wherein the active pharmaceutical ingredient is incorporated in layer of the tablet; (ii) using 0.2 to 30% one mucoadhesive polymer such as cellulose ethers or alginates in layer of the tablet; (iii) 50-98 % excipients such as crystalline and granular diluents which aid flow such as disodium hydrogen phosphate, sodium bicarbonate, magnesium carbonate, mannitol; and (iv) 0.5 to 20 %, more precisely 2 to 10 % stabilizers such as glycine, lysine and their organic and inorganic salts. 2. A transmucosal drug delivery system and its preparation for Benzimidazole class proton pump inhibitors (PPIs) for oral mucosal administration as claimed in claim 1 wherein the said dosage form is prepared by using direct compression, wet granulation and dry granulation technique using the said excipients. 22 A transmucosal drug delivery system and its preparation for Benzimidazole class of proton pump inhibitors for oral mucosal administration as claimed in claim 1 wherein the proton pump inhibitor, the derivative of Benzimidazole class is incorporated in dosage form comprises of 2 to 35 % w/w of the tablet form. A transmucosal drug delivery system and its preparation for Benzimidazole class of proton pump inhibitors for oral mucosal administration of Benzimidazole class of proton pump Inhibitors (PPIs) as claimed in claim 1 wherein the Benzimidazole proton pump inhibitor comprises of 5 to 30% w/w of the dosage form. A transmucosal drug delivery system and its preparation for Benzimidazole class of proton pump inhibitors for oral mucosal administration as cfaimed in claim 1 wherein selected proton pump inhibitors (PPI) of Benzimidazole class are Lansoprazole, pantoprazole, rabeprazole, omeprazole and their therapeutically active precursor, derivative, salts, metabolites or similar active pharmaceutical ingredients. A transmucosal drug delivery system and its preparation for Benzimidazole class of proton pump inhibitors for oral mucosal administration as claimed in claim 1 wherein the mucoadhesive polymers comprises of 1 to 30 % of the dosage form. 23 7. A transmucosal drug delivery system and its preparation for Benzimidazole class of proton pump inhibitors for oral mucosal administration as claimed in claim 1 wherein the mucoadhesive polymers comprises of 5 to 15% of the dosage form. 8. A transmucosal drug delivery system and its preparation for Benzimidazole class of proton pump inhibitors for oral mucosal administration as claimed in claim 1 wherein excipients containing minimum amount of or no sodium ions. 9. A transmucosal drug delivery system and its preparation for Benzimidazole class of proton pump inhibitors for oral mucosal administration as claimed in claim 1 to 8 as substantially herein described with reference to the foregoing description and examples. Dated this on 3rd day of Oct 2003. _ ^ ^^ i-"" ~ ^ Dr. Rajeshkumar H. Acharya. Advocate & latent agent For and on behalf of the applicant. 24

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