Preparation and evaluation of verapamil hydrochloride microcapsules.
Verapamil was encapsulated with ethylcellulose (EC) and cellulose acetate (CA) in various ratios of drug and polymer by the hot melt technique and the prepared microcapsules were evaluated for size range, drug content, drug release profiles, and kinetics of drug release. The microcapsules were compressed into tablets to study the variation of drug release between the 2 types of formulations (ie, microcapsules and tablets). The size analysis of prepared microcapsules was done by a standard sieving method and in vitro dissolution studies were carried out in USP XXI dissolution test apparatus in 0.1 N HCl as dissolution media to study the drug release profiles of the microcapsules. Scanning electron microscopy studies were carried out to investigate the surface characteristics of the microcapsules prepared from both type of polymers. Drug release profiles from the compressed non-disintegrating matrix tablets prepared from the microcapsules were also investigated. All the microcapsules were discrete, free flowing, and reproducible with respect to size distribution and drug content. Maximum percentage of the microcapsules belonged to the size range of 35/50. Drug release durations of VERCA1 (drug: CA 3:1), VERCA2 (drug: CA 2:1), and VERCA3 (drug: CA 1:1) microcapsules were extended up to 3, 5, and 6 hours, respectively, and those of VEREC1 (drug: EC 3:1), VEREC2 (drug: EC 2:1), and VEREC3 (drug: EC 1:1) microcapsules were extended up to 4, 5, and 7 hours, respectively. The microcapsules of both types having a drug:polymer ratio of 1:1 had the slowest release rate in their respective categories. The microcapsules were compressed into nondisintegrating matrix tablets. The hardness of the tablets was tested using the Monsanto Hardness Tester and was found to be 6-7 kg/cm. All the tablets contained the drug verapamil within 100% +/- 5%. The drug release data of both the microcapsules and tablets prepared were examined kinetically, and the ideal kinetic model was determined for the drug release. The tablets prepared by compressing the microcapsule formulations were more satisfactory in releasing the drug at a controlled and uniform rate following Higuchian kinetics and the formulations VCACRT3 and VECCRT3 were able to control release of drug up to 12 hours. Thus, it is possible to formulate a single-unit, controlled-release dosage form of verapamil for oral administration at least once every 12 hours using the polymers CA and EC.
Mukherjee
Biswajit
B
Department of Pharmaceutical Technology, Jadavpur University, Kolkata (Calcutta), India. biswajit55@yahoo.com
Mahanti
Beduin
B
Panda
Prabhudutta
P
Mahapatra
Sushmita
S
D000284:Administration, Oral; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000737:chemistry*; D002214:Capsules; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D012995:Solubility; D013607:Tablets; D014700:Verapamil / Q000008:administration & dosage / Q000737:chemistry*
D000889:Anti-Arrhythmia Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; C005062:acetylcellulose; C013517:ethyl cellulose; D002482:Cellulose; D014700:Verapamil