Ultrastructural evaluation of cold compressed steroid filled-TCPL devices in human plasma

Abstract

Several studies have been carried out on ceramic delivery systems. The majority of these efforts have attempted to utilize the analysis of the capsular tissues and blood serum as a measure of the release rate and behavior. To gain a better understanding of the effect of porosity on the rate of drugs released, the authors have studied the sustained delivery of steroids from a tricalcium-phosphate-lysine steroid delivery system (TCPL) in human plasma as a model for ultrastructural evaluations. A microcrystal of TCP was prepared by following the authors' standard laboratory procedures. Three different steroids (testosterone (T), progesterone (P) and estradiol (E)) were incorporated (individually) into the TCPL matrix. Each matrix contained 60 mg of steroid and the homogeneous material was compressed with a 7400 kg compression load. The total amount of steroid released was monitored spectrophotometrically. Standard sterilized technique was used throughout the entire study. At the end of 1, 2, 3, 5, 7, 14 days of incubation, the capsules were retrieved and prepared for SEM analysis. The results of this study showed that: (1) As previously documented, the TCPL devices were capable of releasing steroids at sustained levels, and the ease of delivery was found to be: P>T>E. (2) At the end of 14 days there was a remarkable increase in the size of micro and macropores observed in all experimental and control capsules. (3) Steroid-filled capsules exhibited a higher (p<0.01) mechanical strength value (78/spl plusmn/16 MPa) compared to the mechanical strength of sham control capsules (43/spl plusmn/14 MPa). The overall conclusion of this study is that the admixture of steroid with ceramic material acted as another binder and contributed tremendously to the higher mechanical strength of the capsules compared to sham controls.