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KMID : 0366919970090010085
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Sungkyun Pharmceutical Journal
1997 Volume.9 No. 1 p.85 ~ p.96
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Influence of physicochemical properties of model compounds on their release from biodegradable polyanhydride devices
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Park, Eun-Seok
Maniar, Manoj/Shah, Jaymin C.
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Abstract
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A new class of fatty acid dimer-based polyanhydride, polycfatty acid dimer-sebacic acid) (P(FAD-SA)), was reported to have desired physicochemical and mechanical properties for a biodegradable device and believed to undergo pure surface erosion. The objectives of this study were to determine if P(FAD-SA) undergoes pure surface erosion, and to identify the factors governing the release characteristics and mechanism from polyanhydride devices at various pHs. Three model compounds, mannitol (small M_w, highly water soluble), inulin (large M_w, moderately water soluble) and stearic acid (medium M_w, extremely lipophilic) were incorporated at 10% w/w in disk-shaped P(FAD-SA, 50:50 w/w) devices and the release of the compounds studied from pH 1-9. All the three model compounds were released faster at alkaline pH than at acidic pH (pH 9＞pH 7.4＞pH 1-5), suggesting that the release of model compounds was dependent on the catalyzed erosion of polyanhydride. However, erosion was not the sole release rate controlling mechanism for these model compounds. Highly water soluble mannitorl and inulin were released rapidly at acidic pH, when erosion of polyanhydride is negligible. Mannitol released faster than inulin, which was released faster than lipophilic stearic acid at all pH, suggesting that the hydrophilic/hydrophobic nature of the loaded compound influenced its release significantly. the observed release profiles were significantly higher, and did not match the release profiles predicted from erosion rates of the mannitol and inulin devices, however they were closer for stearic acid devices. Althoug inulin was released rapidly in the initial phase (40-50%), only 60-70% inulin was released over a 6-week period compared to 100% release of mannitol. The large molecular size of inulin may have hindered its diffusion through water-filled pores and channels observed in the devices during release, which may have resulted in the majority of inulin being still trapped in the devices. Although various contributing factors in overall release were identified, a single release kinetic model could not explain the release profiles of all the loaded compounds under the different pH conditions. The complete release profiles could be decribed by first order kinetics, however the initial release profiles of all the model compounds were described very well by zero order kinetics. The release rates of mannitol and inulin were influenced by both the erosion rates and the intrinsic dissolution rates unlike release rates of stearic acid which correlated closely with erosion rates. This may be due to the fact that different release machanisms, such as diffusion, dissolution and erosion all play a significant role in overall release of compound from this newly developed P(FAD-SA) device. However, the contribution of each process to overall release may vary as a function of pH, the nature of the compound and polymer erosion. In conclusion, the results suggest that P(FAD-SA, 50:50 w/w) is undergoing bulk erosion rather than the desired surface erosion. If it did undergo surface erosion, release characteristics would be independent of the physicochemical nature of the incorporated compound and release kinetics would be zero order from disk-shaped devices irrespective of the nature of the loaded compound.
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KEYWORD
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