Process Optimization for Manufacturing of Poly(D, L-lactide-co-glycolide) Microspheres of Naltrexone

Author(s)

Patel, B., Patel, R.

Author's Affiliation

Abstract

In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique is investigated. The use of different process options and variables to prepare naltrexone microspheres is also studied. Naltrexone microspheres using biodegradable poly(D, L-lactide-co-glycolide) prepared using solvent evaporation technique had a significant amount of residual amount of solvents above allowable safety threshold. To reduce the level of solvents below safety limit in microspheres, process variables were explore, the effect of different process parameters, such as drug/polymer ratio and temperature at which evaporation is carried out, effect of lyophilization process, effect of pore forming agent, effect of final ethanol washing, etc. on the residual level of solvents in microsphere, morphology, total entrapped drug and in vitro drug release of microspheres was studied. The temperature at which the solvent evaporation was carried out did not have any significant impact on reducing the level of residual solvent in the microsphere. Similarly increasing the ratio of drug:polymer ratio did not have a major impact of residual solvents. However, a higher ratio of drug:polymer yielded higher % drug entrapped. Hence, a higher ratio of drug:polymer was selected so that higher entrapment can help in maintaining required % entrapment even with the use of pore forming agent and use of final ethanol washing procedure where % drug entrapment gets down with reduction of the level of residual solvents. With the use of pore forming agents during microencapsulation process helps in producing microspheres with more porous nature which in turn reduces the residual solvents. But as the microspheres are more porous, it also reduces the drug migration yielding lower % entrapped drug level. With the use of final ethanol washing process during microencapsulation process helps in reduces the residual solvents by extracting residual solvents from microsphere. But it also reduces the drug migration yielding lower % entrapped drug level. Wherever microspheres are more porous, % in vitro release also becomes faster. Desired level of residual solvents in microspheres along with required release profiles of naltrexone & % drug entrapped can be achieved using right process variables.

Keywords

Naltrexone, Residual solvent, % drug entrapped, Pore-forming, Ethanol washing process, Temperature, Solvent evaporation

Cite This Article

Patel, B., Patel, R. (2017). Process Optimization for Manufacturing of Poly (D, L-lactide-co-glycolide) Microspheres of Naltrexone. International Journal for Pharmaceutical Research Scholars (IJPRS), 6(2), 69-80.