1. Rationale of the Project:
Several approaches on the preparation of the fast release tablet dosage form has been done in the past. A fast release dosage form releases in the stomach in less than 30 minutes. The theme behind this project is to form a fast release tablet dosage form by using the buffer system. The advantages outstand when rabeprazole is used along with the buffering agents such as sodium bicarbonate and calcium carbonate(2). The buffered system rapidly disintegrates within the aqueous stomach media even if the stomach has minimal motility. Another benefit is that these buffers protect rabeprazole from the degradation of Rabeprazol by HCl in stomach. We can decrease the onset of action to 30 minutes compared to other PPIs (1-2hrs) with the buffered system(2).Due to the acid neutralizing property of the buffer itself, a fast symptomatic relief (60 seconds) can be acquired. The buffered system of Rabeprazole helps to hasten the onset of action over the other enteric coated formulation as it has early Tmax(3.5 hrs).(3) It has the activation half life of 7.2 min which leads to faster PH control and symptom relief as compared to other PPI's
Approaches for fast release of drug formulation:
i. Modification of the drug's lipophilicity such as by esterification of the drug.(1)
ii. Altering the permeability of the gastrointestinal cell membranes by the use of absorption enhancers.(1)
iii. Creating alkaline pH in gastric environment which facilitates the absorption of drug in stomach.(4)
iv. Increasing the solubility of the drug by using the salt form of the drug or incorporating into the formulation a substance that forms a salt with the drug during dissolution.( eg. increase the dissolution of aspirin by using the magnesium oxide in the formulation) (1)
v. Use of the buffered systems and enteric aqueous coating formulations (2)/(3)
2. Rabeprazole-Drug Profile:
Rabeprazole is a Proton-Pump Inhibitor which works by decreasing the secretion of the acid in the stomach by the inhibition of (H/K)-ATPase. It is a substituted benzimidazole used for decreasing gastric acid secretion.(9). It is used to treat ulcers, gastroesophageal reflux disease (GERD), heartburn and Zollinger-Ellison syndrome. Rabeprazole is used in combination with medications like amoxicillin and clarithromycin to eliminate H. pylori, a bacterium that causes ulcers(5)/(7). Rabeprazole used alone is better than any other PPIs for eg, its bioavailability is 52% time dependent and has 10000 folds of acid trapping property compared to that of omeprazole which has only 1000 folds of acid trapping property and 64% time dependent bioavailability(2) .Its high pKa value(4.9) offer the advantage of its 10 times more accumulation compared to other PPIs (eg Omeprazole having pKa of 4.3) in the gastric parietal cell's canaliculi. Rabeprazole inhibits the basal and peptone meal-stimulated acid secretion versus placebo by 86% and 95%, respectively, and increases the percent of a 24-hour period that the gastric pH>3 from 10% to 65% (9). It is only the PPI known to increase the mucous formation. The property of rabeprazole in increasing the formation of the mucous helps in making a barrier between the acid and the underlying tissues. It has no side effects related to gastro intestinal hormones.
3. Aims:
The aim of this project is to formulate Rabeprazole fast release in tablet dosage form, to optimize the drug release profile and evaluate its in-vitro analysis variables.
4. Objectives:
1. To design an Rabeprazole fast release tablets using Sodium bicarbonate and magnesium Oxide etc.
2. To compare the drug release and the release rates from the market product with that of different formulations prepared.
3. To perform in-vitro analysis on drug release rate from the formulated tablets.
4. Ho: There is no difference in the mechanism and rate of drug release from the leading market product with that of different formulations formulated.
5. HA: There is difference in the mechanism and rate of drug release from the market product with that of different formulations formulated.
5. Materials and Machines Required:
5.1 Raw materials:
a) Active Pharmaceutical Ingredients – Rabeprazole sodium,
b) Binder – Hydroxypropyl Cellulose, Low Substituted Hydroxypropyl Cellulose( L-HPC, L-21 )
c) Buffering agents : (Sodium Bicarbonate, Magnesium Oxide and Calcium carbonate)
d) Diluents- Powder Mannitol, Magnesium Oxide,
e) Disintegrant : Low Substituted Hydroxypropyl Cellulose( L-HPC, L-21 ), Croscarmellose Sodium, Sodium Starch Glycollate.
f) Lubricants (P. Talc, Magnesium Stearate)
g) Polymers: Hydroxypropyl
h) Solvents- Methylene chloride, Isopropyl alcohol, Water.
5.2 Reagents:
a) Depends upon analytical procedure developed.
5.3 Equipments and Instruments:
a) Analytical and precision balance
b) Lab model mass mixer
c) Shifter
d) Tray drier/ Fluid Bed Drier
e) IR moisture balance
f) Dehumidifier
g) Tablet compression machine
h) Friability tester
i) Hardness tester
j) Disintegration Test apparatus
k) Dissolution test apparatus
l) UV-Visible spectrophotometer/ HPLC- depend upon analytical procedure.
6. Methodology:
First we take mannitol and crospovidone along with the buffering agents calcium carbonate and sodium bicarbonate, magnesium oxide, low-substituted hydroxypropylcellulose, and magnesium stearate and mix with rabeprazole sodium as a core formulation and follow the wet granulation. The granules are then dried using a fluidised bed drier and then passed through a 1.5 mm screen. Dried granules are blended with the rest of L-HPC and magnesium stearate in a V-blender. Density of the final granulation is then measured with a tapped density tester. The powder mass is then compressed using a compression machine. The uncoated tablets is then subjected to a film coating using a solution ethylcellulose/magnesium oxide(1:1%w/w) dispersion and then with aqueous enteric coating with Acryl EZE which is a aqueous enteric coating based on methacrylic acid copolymer type C. The tablets are then tested for the acid uptake value and the dissolution test is run and the drug release is tested using the HPLC analysis. Then, the release pattern and the dissolution profile our buffered system formulation is compared with the enteric coated conventional marketed products.
6.1 Research design:
• The batches of tablets with minimum batch size of 100 tablets will be taken using the Buffering agent at different concentration.
• The release profile of the first batch will be studied and from its result, subsequent batches will be designed to get the desired characters.
• Tablet compression will be done and their variability will be studied.
6.2 Research Laboratory:
• All the work will be conducted in Qmed Formulation Pvt. Ltd., Chhaling-5, Bhaktapur, Nepal.
6.3 Materials Required and Cost of the Project:
• The Qmed Formulation Pvt. Ltd. has agreed to provide the materials and equipments that are available in the company.
• Other material if required has to be purchased.
• The estimated cost of the project is around 18000/- ( Eighteen thousand only)
7. Conclusion
In this project a new method of enhancing the release profile of the drug, improving the dissolution and decreasing the time of onset of action will be studied. The effects of various concentration of the buffering agents, drug release patents, extent and rate of release will be studied. A validated method for the development of fast release formulation will thus be developed. The formulation will then be compared with the marketed product and the dummy and the conclusion will then be made on the basis of the observation and the data obtained.
References:
1. Aulton Michael E., Aulton's Pharmaceutics The design and Manufacture of Medicines, Third edition, Churchill Livingstone Elsevier Publication, Pg. 455-456
2. Application of a Fully Formulated Aqueous Enteric Coating System on Rabeprazole Sodium Tablets (20 mg)
3. Enteric coated Rabeprazole Sodium and Itopride Hydrochloride sustained
release capsules
4. www.patentdocs.com
5. www.wikipedia/rabeprazole
6. http://www.who.int/medicines
7. http://www.medpedia/rabeprazole
8. The selection and use of essential medicines, WHO Technical Report series, 2009
9. http://www.colorcon/acryl-EZE
10. Raymond C. etal, "Handbook of Pharmaceutical excipients",PhP Pharmaceutical Press, London, ChicagoRaymond C Rowe, Paul J
No comments:
Post a Comment