PubMed · 10234521
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R Bodmeier. 1999. Coating of solid dosage forms.. https://doi.org/10.1016/s0939-6411(98)00092-7
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A digital image analysis method for the estimation of mean pellet size and coating thickness employing optical microscopy was evaluated. The coating thickness was expressed as the difference in mean projected area radius of the uncoated and the coated pellets. The repeatability, the intermediate precision and the robustness of the image analysis method were investigated. The repeatability and the intermediate precision of the image analysis method was excellent with a low degree of scatter between the measurements. The robustness investigation on the image analysis method illustrated the importance of controlling and monitoring the illumination technique utilised. Calibration of the image analysis equipment was of the highest importance. Using pellets with a high degree of sphericity and narrow size distribution, it was sufficient to use 1000 pellets to estimate the mean pellet size and the coating thickness with an accuracy of +/-1.2 microm. An equation is presented for an approximation of the number of pellets necessary to achieve a given accuracy in the estimation of mean pellet size and coating thickness.
Incomplete release and poor stability of encapsulated proteins are common hurdles to overcome when developing poly(lactide-co-glycolide) (PLGA) controlled-release systems. Antacid excipients such as Mg(OH)2, which increase both microclimate pH and polymer water uptake, have been shown to prevent acid-induced instability of proteins encapsulated in PLGA. The purpose of this study was to delineate the effects of microclimate pH and polymer water content on the stability of encapsulated bovine serum albumin (BSA) by comparing the effects of Mg(OH)2 with those of another excipient, sucrose, which increases polymer water content without significantly affecting acid-base chemistry of the polymer. These two excipients, when encapsulated in PLGA at appropriate levels (3% Mg(OH)2 vs. 10% sucrose), were found to cause identical water sorption kinetics, thus allowing the effect of the two microclimate parameters to be determined. In contrast to their similar effects on polymer water sorption, Mg(OH)2 afforded a much greater stabilization effect on encapsulated BSA than did sucrose, with less than 7% aggregates for 3% Mg(OH)2 compared to 51% for 10% sucrose and 81% without either excipient after 4 weeks of incubation at 37 degrees C. When the protein stabilization rationale of neutralizing the acidic microenvironment by adding Mg(OH)2 was applied to the delivery of an important therapeutic protein, tissue plasminogen activator (t-PA), t-PA stability was also improved and the active protein was completely recovered during a one month period of in vitro release. These data demonstrated that although increased water uptake induced by antacid excipients may improve the stability of the encapsulated proteins, the homogeneous acid neutralization effect is unique to antacid excipients such as Mg(OH)2, which is necessary to maintain the stability of proteins in acidic PLGA specimens.
The elastic and viscoelastic properties of pellets and film coatings applied to pellets were studied using Dynamic Mechanical Analysis (DMA). Four batches of spherical pellets produced with different methods were compared without film coating and after application of a plasticised ethylcellulose film of average thickness of 25 microm. The modulus of elasticity of the uncoated pellets was found to be related to the porosity of the pellets, as was the slope of the linear portion of the storage modulus-dynamic force curves. None of the other parameters obtained from DMA of the uncoated pellets appeared to be related to the macroscopic properties of these pellets. After application of the film coating the dynamic force at the onset of the linear portion of the storage modulus-dynamic force curve and the maximum storage modulus obtained at a dynamic force of 600 mN were found to be significantly different from the values of the uncoated pellets, but similar for all four coated pellet batches. Hence these parameters represented the viscoelastic behaviour of the film coatings.