Preparation and characterizationin vitro of sustained-release captopril/Chitosan-gelatin net-polymer microspheres (Cap/CGNPMs)

Abstract

The captopril/Chitosan-gelatin net-polymer microspheres (Cap/CGNPMs) were prepared using Chitosan (CS) and gelatin (Gel) by the methods of emulsification. A cross linked reagent alone or in combination with microcrystalline cellulose (MCC) was added in the process of preparation of microspheres to eliminate dose dumping and burst phenomenon of microspheres for the improvement of the therapeutic efficiency and the decrease of the side effects of captopril (Cap). The results indicate that Cap/CGNPMs have a spherical shape, smooth surface morphology and integral inside structure and no adhesive phenomena and good mobility, and the size distribution is mainly from 220 to 280 μm. Researches on the Cap release test in vitro demonstrate that Cap/CGNPMs are of the role of retarding release of Cap compared with Cap ordinary tablets (COT), embedding ratio (ER), drug loading (DL), and swelling ratio (SR), and release behaviors of CGNPMS are influenced by process conditions of preparation such as experimental material ratio (EMR), composition of cross linking reagents. Among these factors, the EMR(1/4), CLR (FOR+TPP) and 0.75% microcrystalline cellulose (MCC) added to the microspheres are the optimal scheme to the preparation of Cap/CGNPMs. The Cap/CGNPMs have a good characteristic of sustained release of drug, and the process of emulsification and cross-linking process is simple and stable. The CGNPMs is probable to be one of an ideal sustained release system for water-soluble drugs.

Keywords

captopril / chitosan / gelatin / microsphere / drug sustained release

References

[1] Romankiewjcz J. Captopril: An Update Review of Its Pharmacological Properties and Herapeutic Efficacy in Congestive Heart Failure [J]. Drugs, 1983, 25: 6-21.

[2] Tian W R, Gao Z, Wang S X. Studies of Captopril of Pharmacokinetics on Health Human Body [J]. Chin. Hosp. Pharm. J., 1993, 13: 55-56.

[3] Seta Y, Higuchi F, Kawahara Y, . Design and Preparation of Captopril Sustained-release Dosage Forms and Their Biopharmaceutical Properties [J]. Int. J. Pharm., 1988, 41: 245-254.

[4] Anaizi N H, Swenson C. Instability of Captopril Solution [J]. Am. J. Hosp. Pharm., 1993, 50: 486-488.

[5] Abubakr O N, Zhang J S. Recent Progress in Sustained/Controlled Oral Delivery of Captopril: An Overview [J]. Int. J. Pharma., 2000, 194: 139-146.

[6] Tsai T, San Y P, Ho H O, . Film-forming Polymergranulated Excipients as the Matrix Material for Controlled-release Dosage Forms [J]. J. Control. Release, 1998, 51: 289-299.

[7] Zhang S Q, Xie Y, Hao Z H, . Studies of Captopril Sustained Release Tablets [J]. Chin. Pharm. J., 1996, 31: 668-669.

[8] Kawashima Y, Handa T, Kasai A, . Novel Method for the Preparation of Ncontrolled-release Theophylline Granules Coated with a Polyelectrolyte Complex of Sodium Polyphosphate-chitosan [J]. J. Pharm. Sci., 1985, 74: 264-268.

[9] Yao K D, Yin Y J, Xu M X. Studies of Release Behavior of Chitosan/Gelatin Net Polymer Microsphere [J]. Chin. Sci. Bull., 1995, 40: 2 241-2 243.

[10] Wang Y M, Shi T S. Process in the Studies of Controlled Release of Microsphere Formulation [J]. Chin. Pharm. J., 1996, 31: 131-134.

[11] Shu X Z, Zhu K J. Controlled Drug Release Properties of Ionically Cross-linked Chitosan Microspheres: the Influence of Anion Structure [J]. Int. J. Pharma., 2002, 233: 217-225.

[12] Chen M X, Mou R X, Ying X H, . Determination of Residual Formaldehyde in Grain Foods by High-performance Liquid Chromatography [J]. Chin. J. Anal. Lab., 2004, 23(5): 74-76.

[13] Ren X, Xu X P, Liao L Y, . Capillary Gas Chromatographic Determination of Seven Residual Organic Solvents in Cefoselis Hydrogen Sulfate and Prulixacin [J]. Chin. J. Antibiot., 2004, 29(6): 354-356.

[14] Wang H, Wu N Y, Ye C Y, . Determination of Seven Organic Solvents in Nicergoline by Headspace Capillary Gas Chromatography [J]. Chin. J. Anal., 2004, 24(3): 273-275.

[15] Liu L S, Thompson A Y, Heidaran M A. An Osteoeonduedve Collagen/Hyaluronate Matrix for Bone Regenerate [J]. Biomaterials., 1999, 20: 1 097-1 108.

[16] Gallo J M, Hung C T, Perrier D G. Analysis of Albumin Microsphere Preparation [J]. Int. J. Pharm., 1984, 22: 63-68.

[17] Nishioka Y, Kyotani S, Masui H. Preparation and Release Characteristics of Cisplatin Chitosan Microspheres and Effect of Containing Chitin and Treated with Chitosan [J]. Chem. Pharm. Bull., 1989, 37: 3 074-3 088.

[18] Nishioka Y, Kyotani S, Okamura M. Release Characteristics of Cisplatin Chitosan Microspheres and Effect of Containing Chitin [J]. Chem. Pharm. Bull., 1990, 38: 2 871-2 890.