Preparation of Parenteral in situ Gel Formulation Based on smart PLGA polymer: Concepts to Decrease Initial Drug Burst and extend drug release

Ahmed, Tarek A.; Hussain, Zahid

doi:10.5599/obp.14.1

Cited by 1 publication

(1 citation statement)

References 51 publications

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“…The ISGI systems are triggered through different transformation mechanisms, such as in situ cross-linking [30], in situ solidifying organogels [31], or in situ phase separation. The phase separation may be based on various factors, for example, temperature change [32], pH change [33], solvent exchange [34] or light [35]. Solvent exchange-induced phase separation mechanism is commonly used in drug delivery research as it can be easily triggered requiring only an aqueous environment [36].…”

Section: Introductionmentioning

confidence: 99%

Investigation of Alogliptin-Loaded In Situ Gel Implants by 23 Factorial Design with Glycemic Assessment in Rats

et al. 2022

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The aim of the study was to design injectable long-acting poly (lactide-co-glycolide) (PLGA)-based in situ gel implants (ISGI) loaded with the anti-diabetic alogliptin. Providing sustained therapeutic exposures and improving the pharmacological responses of alogliptin were targeted for achieving reduced dosing frequency and enhanced treatment outputs. In the preliminary study, physicochemical characteristics of different solvents utilized in ISGI preparation were studied to select a proper solvent possessing satisfactory solubilization capacity, viscosity, water miscibility, and affinity to PLGA. Further, an optimization technique using a 23 factorial design was followed. The blood glucose levels of diabetic rats after a single injection with the optimized formulation were compared with those who received daily oral alogliptin. N-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO), as highly water-miscible and low viscous solvents, demonstrated their effectiveness in successful ISGI preparation and controlling the burst alogliptin release. The impact of increasing lactide concentration and PLGA amount on reducing the burst and cumulative alogliptin release was represented. The optimized formulation comprising 312.5 mg of PLGA (65:35) and DMSO manifested a remarkable decrease in the rats’ blood glucose levels throughout the study period in comparison to that of oral alogliptin solution. Meanwhile, long-acting alogliptin-loaded ISGI systems demonstrated their feasibility for treating type 2 diabetes with frequent dosage reduction and patient compliance enhancement.

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