FORMULATION AND EVALUATION OF

RABEPRAZOLE BUCCOADHESIVE TABLETS

Under the guidance of T.Ramya krishnaM.phram(Ph.d) MD.ImranM.phram(Ph.d)

Presentsed by A.Archana

CONTENTS
Introduction
Literature review Drug profile Excipients profile Plan of work Materials Method Equipments required Conclusion Reference

INTRODUCTION

Oral administration is the most suitable and convenient route for the most of the drugs. But,after oral drug administration many drugs are subjected to pre systemic clearance in the liver. Within the oral route,the oral cavity is an attractive site for drug delivery due to ease of administration and avoids possible drug degradation in the gastro intestinal tract as well as hepatic first pass metabolism. So,buccal drug delivery is attractive alternative to the oral route of drug administration.

Within the oral mucosal cavity, delivery of drugs is classified into three categories. (i) Sublingual delivery, which is systemic delivery of drugs through the mucosal membranes lining the floor of the mouth. (ii) Buccal delivery, which is drug administration through the mucosal membranes lining the cheeks (buccal mucosa). (iii) Local delivery, which is drug delivery into the oral cavity.

Definition: Buccal delivery is defined as drug administration through the mucosal membranes lining the cheeks (buccal mucosa). General criteria for selection of drug candidate: Drug must undergo first pass effect or it should have local effect in oral cavity. Molecular weight should be less than 500 g/mol (Daltons). The maximal duration of buccal delivery is approximately 48 hr. Drugs with low oral bioavailability will be preferable for buccal drug delivery systems

ADVANTAGES
These can be administered to patients with: Ease of administration. Nausea and vomiting, gastrointestinal disease or surgery and/or Ease of administration, Unconscious patients. Moreover, rapid cellular recovery and achievement of a localized site on the smooth surface of the buccal mucosa for a prolonged period of time. Direct access to the systemic circulation through the internal jugular vein by passes drugs from the hepatic first pass metabolism leading to high bioavailability. Reduction in dose can be achieved, there by reducing dose dependent side effects.

LIMITATIONS

Only drugs with a small dose requirement can be administered. Drugs, which are unstable at buccal pH, cannot be administered by this route. Drugs, which irritate the mucosa or have a bitter or unpleasant taste or an obnoxious odour, cannot be administered by this route. The continuous secretion of saliva (0.52 l/day) leads to subsequent dilution of the drug. Sometimes they show unpredictable bioavailability.

LITERATURE REVIEW

Choi HG and Kim CK et al.,(2000) concluded that two omeprazole tablets composed of [omeprazole/sodium alginate/HPMC/magnesium oxide (20/24/6/50mg/tab)] and [(20/30/0/50mg/tab)], which could be attached onto the human cheek without collapse and could stabilize omeprazole in human saliva for at least 4 hours, are potential candidates for omeprazole buccal adhesive tablets. Kumaresan C.et al(2008)., demonstrated different ways for the formulation of the oral dispersible tablets and how the product performance depends on the drug suitability and excipients selections in the delivery system. He described the ideal characteristics of the drug and examples of excipients required in the oral dispersible formulation, taste masking methods and manufacturing methods.1

Yamamoto Y, et al(2009)., demonstrated the relation between powder characteristics and disintegration time of tablets in the mouth (DTM) revealed that a high bulk density results in a short DTM. Tablets producing a DTM less than 60s were obtained when the powder bulk density was greater than 0.5g/mL. They have also demonstrated that the tablets with a short DTM value tended to possess low hardness; however, the use of high-compressibility excipients in the formulation increased the hardness to values greater than 3kg.

S.Ramakrishna et al.,(2011):Rabeprazole pellets prepared by direct punch method.He used four polymers namely hydroxy propyl methyl cellulose k4m,sodium carboxy methyl cellulose,carbopol-934p and ethyl cellulose used for preparation of tablets,which are intended for prolong action may be dew to attachment with intestinal mucosa for relief from active duodenal ulcer.sodium carboxy methyl cellulose showed above 95% release within 10hrs,whereas carbopol934p showed slow release about 88%to92% over a period of 12h excellent muco adhesive strength.Thus the present study concluded that,carbopol-934p mucoadhesive tablets of rabeprazole pellets can be used for localaction in the ulcer diseases as well as for oral controlled release drug delivery.

Shammi G et al.,(2011): they had collected the information about the glipizide, that it is a second generation sulfonyl urea, an oral hypoglycemic agent for the management of non-insulin dependent diabetes mellitus. Oral delivery of glipizide shows bioavailability problems and causes hypoglycemia with gastric disturbances. Solubility of glipizide increases with increase in pH. Glipizide will act by stimulating the insulin secretion from pancreatic beta-cells.4 Arya RK et al.,(2011) they developed and evaluated mucoadhesive tablets of salbutamol sulphate by non-aqueous granulation method by using HPMC K4M and chitosan in different ratios. The prepared tablets were evaluated for weight variation, hardness, thickness and drug content uniformity. Tablets prepared with increased ratio of HPMC K4M showed higher swelling index than tablets prepared with decreased ratio of HPMC K4M. In-vitro bio adhesive strength studies showed that tablets containing less HPMC K4M were excellent in bio adhesive nature.5

Jignyashs Raval et al(2012).,

The aim was to prepare and evaluate bucco adhesive tablets of rabeprazole sodium that avoid gastric irritation and first pass effect,thereby increasing the drug bioavailability and onset of action.Take different ratios of Gantrez ms955 along with Hpmc k4m were studied bioadhesive strength.Result found that increase in prehydration time decrease in bioadhesive strength and increase in contact time increased bioadhesive strength,thus a stable buccoadhesive formulation optimized.

DRUG PROFILE
Name: Rabeprazole Category: anti-ulcer agent enzyme-inhibitors Description: rabeprazole is an anti-ulcer drug in the class of proton pump inhibitors.It is a prodrug ,in the acid environment of parietal cells turns into active sulphenamide form. Solubility: soluble in water.

Mechanism of action: It suppress the gastric acid secretion by inhibiting the gastric hydrogen-pottasium adenosine triphosphatase at the secretory surface of the gastric parietal cells. Pharmacokinetics: Absorption: absolute bioavailability is approximately 52%. Metabolism: hepatic. Elimination: eliminated in the urine. Half life: 1-2 hours (in plasma)

EXCIPIENT PROFILE:
Carbapol: Molecular formula: -CH2-CH-N-COOH Synonyms: Carbomer/carbopol 934, 940, 941 Chemical name: carbopol 934(carboxy vinyl polymer 934)

Description: It is a synthetic high molecular weight cross linked polymers of acrylic acid. Appearance: white fine free flowing powder.

Micro crystalline cellulose:

Synonyms: cellulose gel, crystalline cellulose. Functional category: Tablet and capsule diluents, Tablet disintegrate, Suspending, Viscosity-increasing agent.

Structure of mcc:

solubility: insoluble in water, dilute acids,slightly soluble in sodium hydroxide solution.

Stability and Storage Conditions: Stable, hygroscopic store in well closed container. Applications in Pharmaceutical Technology: Tablet binder/diluents 5-20% concentration Tablet disintegrants 5-15% concentration Tablet glidant 5-15% concentration Anti-adherent 5-20% concentration Adsorbent Capsule diluents 10-30% concentration.

Magnesium Stearate
Nonproprietary Names: BP: Magnesium stearate PhEur: Magnesii stearas USPNF: Magnesium stearate Synonyms: Magnesium octadecanoate, octadecanoic acid, magnesium salt, stearic acid. Functional Category: Tablet and capsule lubricant.

Description: Magnesium stearate is a very fine, light white, powder of low bulk density, having a faint odour of stearic acid and a characteristic taste. The powder is greasy to the touch and readily adheres to the skin. Solubility: Practically insoluble in ethanol, ethanol (95%), ether and water, slightly soluble in warm benzene and warm ethanol (95%).

Applications in Pharmaceutical Formulation: Magnesium stearate is widely used in cosmetics, foods and pharmaceutical formulations. It is primarily used as a lubricant in capsule and tablet manufacture at concentrations between 0.25% and 5.0% w/w. It is also used in barrier creams. MANNITOL Synonyms:D-mannite,mannite Functional category: Diluent,plasticizer,sweeting agent. Applications:mannitolis commonly used as an excipient in the manufacture of chewable tablet formulations because of its negative heat of solution,sweeetness. Description: mannitol occurs as a white,odourless,crystalline powder,or free flowing granules.

PLAN OF WORK
AIM:Formulation and evaluation of rabeprazole buccoadhesive tablets Evaluated parameters Hardness Thickness Dissolution Permeation studies Adhesion strength Swelling index Drug residence time Objective:The objective of the study was to prepare and evaluate bucco-adhesive tablets of rabeprazole sodium that avoid gastric degradation and first pass metabolism, thereby increasing the drug bioavailability and onset of action.

MATERIAL USED
Rabeprazole Carbopol Micro crystalline cellulose Mannitol Magnesium stearate

METHOD
Direct compression method: Direct compression is by far the easiest means of processing tablets. Because it only involves the main steps of powder blending, lubrication, and compaction. Because there is no granulation step to improve flow and compaction it is usually necessary to use excepients specifically designed for direct compresion,and engineered to provide the necessary flow and compaction properties.

EQUIPMENTS REQUIRED
Electronic single pan balance sartorius- Mumbai Dissolution test apparatus lab india- Mumbai UV- visible spectrophotometer- lab india Mumbai Tablet punching machines(10 stations) Hardness tester(Electrolab) Hplc(schimadzu) Franz diffusion cell physical balance -Lab india.

Based on the literature review collected various formulations to be carried out to optimized the formulation and evaluation parameters Permeation studies Hard ness Thickness Dissolution Bio adhesion strength Swelling index

REFERENCES

Choi HG, Kim CK. Development of omeprazole buccal adhesive tablets with stability enhancement in human saliva. Journal of Controlled Release 2000; 68: 397-404. C.Kumaresan. Orally Disintegrating Tablet-Rapid Disintegration, Sweet Taste, And Target Release Profile. 2008 Sep;6(5). Yamamoto Y, Fujii M, Watanabe K, Tsukamoto M, et al. Effect of powder characteristics on oral tablet disintegration. International Journal of Pharmaceutics 2009;365:116-120.

S.Ramakrishna.formulation and evaluation of rabeprazole sodium mucoadhesive tablets for duodenal ulcer.international journal of medical and pharmaceutical sciences,vol01(06),2011. Shammi G, Jitendra Kumar Rai, Narang RK, Rajesh KS. Sulfonyl ureas for antidiabetic therapy, an overview for glipizide. Int J Pharmacy Pharm Sci 2010;2(2):01-06. Arya RK, Chaurasia H, Bharadwaj P, Garud N, Palani S. Development and evaluation of mucoadhesive buccal tablets of salbutamol sulphate. Int Res J Pharm 2011;2(1):159-62. Jignyasha raval.formulation and process optimization of buccoadhesive tablet of rabeprazole.international journal of pharmaceutical and chemical sciences,vol1(issue1),janmar2012.