Temporal Precision in Antidiabetic Drug Delivery: Development and Evaluation of a Dual-Drug Pulsatile System for Metformin and Linagliptin

Abstract

This study showed that ML-PULSE which is a new pulsatile drug delivery system (PDDS) applied the concept of bioavailability to release drug in time with circadian rhythms to regulate Type 2 diabetes. Metformin HCl (MP4) and Linagliptin (LP5) were taken as model drugs. Preformulation analysis confirmed high solubility of Metformin and moderate solubility of Linagliptin which were then applied to carry out formulation modifications. The UV-Vis absorbance of the two drugs at 232 nm was similar and thus was accurate in quantification. Optimal formulations were derived, and the particle sizes were nanometric, entrapment efficiency was very high, and lag times were precise (3 hours MP4, 2.5 hours LP5), and about 88% of the drug was released in 12 hours. The in-vitro research design depicted zero-order release of Metformin and Korsmeyer-Peppas kinetics of Linagliptin. Pharmacokinetic studies in diabetic rats showed that AUC 0-infinity had gone up significantly, Tmax was delayed, half-life was extended and the rate of elimination was decreased which was in support of chronotherapy. There was in-vivo efficacy which showed considerable improvement in glucose regulation, insulin sensitivity and tissue protection. The results of the stability test were confirmed and determined to be very intact even in accelerated and long-term environment. ML-PULSE was found to be a potential two-drug PDDS which offered more glycemic control.