You are hereFORMULATION AND IN VITRO EVALUATION OF METOCLOPRAMIDE HYDROCHLORIDE MICROSPHERES PREPARED BY SOLVENT EVAPORATION METHOD

FORMULATION AND IN VITRO EVALUATION OF METOCLOPRAMIDE HYDROCHLORIDE MICROSPHERES PREPARED BY SOLVENT EVAPORATION METHOD


About Authors:
Mubarak Patel*, Suresh. V. Kulkarni,
Department of Pharmaceutics,
Sree Siddaganga College of Pharmacy,
B. H. Road, Tumkur-572102, Karnataka, India.

*patel.mubarak2@gmail.com

ABSTRACT:
The purpose of the research work was to prepare and evaluate the microspheres of metoclopramide hydrochloride as a model drug by solvent evaporation method with carbopol and HPMC polymers in various proportions. A total of six formulations were prepared i.e. F1, F2, F3, F4, F5 and F6. The microspheres were evaluated for micromeritic properties, particle size, % yield, Drug content and Drug release. The size or average diameter of prepared microspheres were recognized and characterized by scanning electron microscopic methods. Microspheres were found discrete, spherical and free flowing. They ranged in particle size from 45.6- 52.2 μm. Metoclopramide hydrochloride release from these microspheres was slowed, extended and depended on the type of polymer used. The formulation F2 and F5 showed consistent drug release for up to 12 h time period. Among all the formulations, F2 contains carbopol 934 and F5 containing HPMC showed the reproducible results with best release profile and good surface morphology. Release data were analyzed based on Highuchi kinetics and Korsmeyer/Peppa’s equation and all the selected formulations showed good fit to Peppa’s equation. The work has demonstrated that among all the formulations of microspheres, particularly those of formulation F2 are promising candidates for the sustained release of metoclopramide hydrochloride in the gastrointestinal tract.

Reference Id: PHARMATUTOR-ART-1321

INTRODUCTION:
Despite of tremendous advancements in drug delivery, Oral routes of drug administration have wide acceptance up to 50-60% of total dosage forms due to ease of ingestion, pain avoidance, versatility (to accommodate various types of drug candidates), and most importantly patient compliance. Also, solid oral delivery systems do not require sterile conditions and are, therefore, less expensive to manufacture1,2. Microspheres in general, have the potential to be used for targeted and controlled release drug delivery. Microencapsulation for oral use has been employed to sustain the drug release and to reduce or eliminate gastrointestinal tract irritation. In addition, multiparticulate delivery systems spread out more uniformly in the gastrointestinal tract. This result in more reproducible drug absorption and reduces local irritation when compared to single-unit dosage forms such as no disintegrating, polymeric matrix tablets. Microencapsulation is used to modify and retard drug release. Due to its small particle size, are widely distributed throughout the gastrointestinal tract which improves drug absorption and reduces side effects due to localized build-up of irritating drugs against the gastrointestinal mucosa.3,4. The conventional dosage forms of metoclopramide hydrochloride (MCP) contains drawbacks like dose related side effects like chills, dizziness, convulsions, irregular heartbeat, headache, abdominal pain and loss of appetite. It’s higher solubility in water results in burst effect with sudden peak levels of drug in blood. Though it is well absorbed undergoes a significant first pass metabolism which may reduce the systemic bioavailability up to 30%. It needs 3-4 times daily dosing which may leads to non-compliance. It is a commonly prescribed drug used for the management of gastrointestinal disorders such as gastric stasis, gastroesophageal reflux and for the prevention of cancer chemotherapy-induced emesis. It is a potent antiemetic and prokinetic, used in the treatment of certain disorders of the digestive tract. The drug has a short biological half-life (4±1h) and is usually administered in a dose of 10-15 mg given up to 4 timesdaily in order to maintain effective concentration throughout the day. Therefore the development of sustained release microspheres would clearly be advantageous. Moreover the site of absorption of MCP is stomach and dosage form that is retained in the stomach would increase the absorption.  A sustained-release formulation that makes twice daily administration of MCP possible might be an advantageous dosage form, especially in long term therapy5, 6, 7. Carbopol 934 has been selected as a polymer in the preparation of microspheres because of its good mucoadhesive properties and is not absorbed by body tissues and being totally safe for human oral consumption. Hydroxy propyl methyl cellulose (HPMC) as a release retarding material. The aim of present study was to develop and evaluate sustained release microspheres of metoclopramide hydrochloride using Carbopol 934 and HPMC as polymer and emulsion-solvent evaporation as a method of preparation and to evaluate the effect of various formulation variables on the physical characteristics, drug content as well as the in Vitrorelease profiles of the microspheres. Metoclopramide hydrochloride whose physicochemical properties and short half life (4±1 hrs) make it suitable candidate for sustained release drug delivery system.

MATERIALS AND METHODS:

Materials
Metoclopramide hydrochloride was received as gift sample from Vaikunth Chemicals, Ankleshwar, Carbopol-934 and HPMC was purchased from Loba Chemie Pvt. Ltd. Mumbai., Ethanol, Tween 80, dichloromethane and Heavy Liquid Paraffin was obtained from SD fine chemicals Ltd., Mumbai (India). All other chemical and reagent used in this study were of analytical grade.

Method of preparation4:-
Six batches of microspheres were prepared by taking drug: polymer ratio as 1:1, 1:1.5 and 1:2 with MCP as drug and two different polymers. The formulation batches were designated as F1, F2, F3 for Carbopol 934  (1:1, 1:1.5,1:2 respectively) and F4, F5, F6 for HPMC (1:1, 1:1.5,1:2 respectively). Drug and polymer in different proportions were weighed and co?dissolved at room temperature into a mixture of ethanol and dichloromethane (1:1% v/v) with vigorous agitation to form uniform drug-polymer dispersion. This was slowly poured into the dispersion medium consisting of heavy liquid paraffin (50ml) containing 1.5% Tween 80. The system was stirred using over head propeller agitator at a speed of 400 rpm at room temperature over a period of 2-3 hrs, to ensure complete evaporation of the solvent. Liquid paraffin was decanted and the microspheres were separated by filtration through a whatmann filter paper, washed thrice with 180 ml of acetone and air dried for 24 hrs.

Formulation Code

Drug Polymer Ratio

Drug (mg)

Carbopol 934     (mg)

HPMC (mg)

Dichloromethane (ml)

Methanol (ml)

F1

1:1

500

500

-

10

10

F2

1:1.5

500

750

-

10

10

F3

1:2

500

1000

-

10

10

F4

1:1

500

-

500

10

10

F5

1:1.5

500

-

750

10

10

F6

1:2

500

-

1000

10

10

Table -1:- Composition of various MCP microspheres formulations

Dose Calculation8:

The dose of MCP is 10-15 mg four times a day. But the dose is reduced to 40 mg for formatting sustained release microspheres.

Dt = Di (1+ 0.693× tm / t1/2)

Where, Dt = total dose;
Di = initial dose;
tm = time to which the drug is sustained;
t1/2 = half life of the drug.

Dt = 15 (1+ 0.693×12/5)

Dt = 39.948≈40 mg

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