Investigation of controlled drug release from hydroxyapatite tablets

Controlled drug delivery systems (CDDS) are one of the frontier areas of science and used for administration of a pharmaceutical compound in a controlled manner to achieve a therapeutic effect in humans or animals. The objectives of the present study was to formulate, characterize, in vitro drug release from blend of Hydroxyapatite (HAP)/ Hydroxypropyl methylcellulose (HPMC)/Microcrystalline cellulose (MCC) biodegradable tablet loaded with cefazolin sodium to achieve the controlled drug release system. Cefazolin sodium is an antibiotic, used as a pharmaceutical active substance. It shows limited effectiveness when used with conventional applications. Local delivery of cefazolin is desired in conditions such as osteomyelitis, soft-tissue infection and for prevention of post-surgical infections. Therefore, the placement of an antibiotic containing biodegradable drug delivery system do not only provide high sustained concentrations locally in the bone and skeletal tissue, but also decreased hospitalization, and avoidance of parenteral administration. In this work, HAP, hydrophilic polymer HPMC and hydrophobic biopolymer MCC were used for controlled drug delivery system. HAPwhich is highly biocompatible and bioactive bioceramic has been widely used in various clinical applications for repairing bone defects in dental and orthopedic sites. Hydrophilic matrices are most widely used because of its simplicity in manufacture. In this work the hydrophilic polymer, hydroxypropyl methylcellulose is used for extended release formulations. The amount of cefazolin sodium was kept constant in all formulations. However, various formulations were prepared by changing the amounts of polymers and HAP in the tablets. Slow drug dissolution was obtained when 27.5% w/w of HPMC was present in the tablet formulation. It was observed that the amount of HAP creates non-significant changes on the releasing rate while tablets were prepared by direct pressing of the dry mixtures. To increase to effect of HAP on drug release, the method of wet granulation was used. The releasing rate was decreased and the burst effect was retarded by using wet granulation method. The drug release mechanism of cefazolin sodium from HPMC added tablets was described by Pappas's equation. The kinetic behavior of all tablets' formulations indicated a non-Fickian release which is parallel to the swelling featured matrix structure. The "n" values obtained from equation for matrices were between 0.46 to 0.80, indicating an anomalous behavior corresponding to diffusion, erosion and swelling mechanism.