Korsmeyer et. al. (1983) derived a simple relationship which described drug release from a polymeric system (following equation). To find out the mechanism of drug release, first 60% drug release data was fitted in Korsmeyer–Peppas model: Mt / M∞ = ktn Where Mt / M∞ is fraction of drug released at time‘t’ and ‘k’ is the rate constant. Here ‘n’ is the release exponent (M Harris Shoaib et. al., 2006). It is shown that this equation can adequately describe the release mechanism of drugs or other solutes from slabs, spheres, cylinders and discs (tablets), regardless of the release mechanism. It is shown that in case of pure fickian release the exponent ‘n’ have the limiting values of 0.50, 0.45 and 0.43 for release from slabs, cylinders and spheres respectively. For tablets and depending on the aspect ratio i.e., the ration of diameter to thickness, the Fickian diffusion mechanism is described by 0.43 < n < 0.50. For drug release from spherical polymer matrix of a wide distribution, the value of the exponent n for Fickian diffusion depends on the width of the distribution (Ritger and Peppas, 1986). When the release pattern goes for log time versus logarithm of cumulative fraction released then the kinetics termed as KorsmeyerPeppas. 3.3.1. Metoprolol Tartrate Release Kinetics from DL-PLA In Situ Implants: Effect of Excipients Pharmaceutical Dosage Forms contain both pharmacologically active compounds and excipients added to aid the formulation and manufacture of the subsequent dosage form for administration to patients (Raymond C Rowe et. al., 2003). Excipients have various effects on drug release profile. The rate and extent of drug release from in situ implants can be controlled by the use of excipients in the formulation. These agents can act as rate modifier by increasing or retarding the rate of release depending upon the nature of the agent. They probably extent their effects by influencing the way of formulation coagulate after injection into the aqueous medium and therefore on the release characteristics of the sustained release injectables formed in situ (Swarnali Islam, 2008). Metoprolol Tartrate release was studied for 30 days for all excipients with 2% drug load. Result of in vitro release profile parameters are summarized in the Table 3.2 and also graphically represented in the Figure 3.16-3.19 as compared to drug only implant. Table 3.2: Overview of parameters describing the in vitro Metoprolol Tartrate release profiles from in situ DL-PLA implants to see the effects of excipients. Excipients Calculated Drug release Calculated Calculated with 5% Drug time (Day) for during initial time interval time (Day) Load Initial Burst Burst Phase (%) (Day) for for 100 % Linear Phase drug release Gleceryl Mono Stearate Mg Stearate Stearyl Alcohol Ceto Stearyl Alcohol Arachis Oil Stearic Acid Cetyl Alcohol Drug without Excipient
0.042
60.16
0.042-7
7
0.042 0.042
63.58 67.84
0.042-5 0.042-3
5 3
0.042
61.93
0.042-7
7
0.042 0.042 0.042 0.042
55.29 63.55 79.74 62.341
0.042-7 0.042-7 0.042-3 0.042-5
7 7 3 5