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A Novel Salted-out and Subsequently Crosslinked Poly(Lactic-co-Glycolic Acid) Polymeric Scaffold Applied to Monolithic Drug Delivery

Department of Pharmacy and Pharmacology, University of the Witwatersrand 7 York Road, Parktown, Johannesburg, South Africa

Viness Pillay

Department of Pharmacy and Pharmacology, University of the Witwatersrand 7 York Road, Parktown, Johannesburg, South Africa, viness.pillay{at}wits.ac.za

Yahya E. Choonara

Department of Pharmacy and Pharmacology, University of the Witwatersrand 7 York Road, Parktown, Johannesburg, South Africa

Clement Penny

Department of Medical Oncology, University of the Witwatersrand 7 York Road, Parktown, Johannesburg, South Africa

This study involved a statistical approach to develop a mechanistic understanding of the salting-out of poly(lactic-co-glycolic acid) (PLGA) and to evaluate the capacity to modulate the physicochemical and physicomechanical properties of PLGA by incorporating electrolytes that produce stochastic fluctuations. The correlation between the three types of salts used and the extent of PLGA chain transitions were established by structural-thermal analysis. Drug-loaded monolithic matrices are prepared by direct compressing salted-out PLGA and a model drug (melatonin). PLGA scaffolds possess fiber diameters and volumes ranging between 0.1—15 µm and 0.0075—14,000 µm³ , respectively. Texture profile analysis reveal a significant increase in the energy absorbed and matrix resilience with increased NaCl₂ and AlCl₃ concentrations. In vitro drug release studies were performed in phosphate buffered saline (pH 7.4; 37°C); the release media was sampled at pre-determined intervals and analyzed by UV spectroscopy. Ideal zero-order drug release profiles were observed with 20% melatonin over a 30-day period. Monolithic matrices prepared by crosslinking melatonin with PLGA reveal a superior capability to control drug release. The salting-out and subsequent crosslinking of PLGA significantly modified the physicochemical and physicomechanical properties of native PLGA and demonstrated the ability to achieve controlled drug release.

Key Words: controlled drug release • salting-out • crosslinking • poly(lactic co-glycolic) acid • (PLGA)3 Box—Behnken design • physicochemical • physicomechanical • textural profiling.

Journal of Bioactive and Compatible Polymers, Vol. 23, No. 2, 132-153 (2008)
DOI: 10.1177/0883911507088274


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