Formulation, Characterization, and Evaluation of Eudragit-Coated Saxagliptin Nanoparticles Using 3 Factorial Design Modules

Abstract

Background and Introduction: Saxagliptin is a hypoglycemic drug that acts as a dipeptidyl peptidase-4 (DPP-4) inhibitor and is preferably used in the treatment of Type 2 Diabetes Mellitus (T2DM). It is safe and tolerable; however, the major disadvantage associated with it is its low bioavailability. Aim: The present research aimed to enhance the bioavailability of the drug by enteric coating with a polymer that controls the rate of drug delivery, and it was prepared as Solid Lipid Nanoparticles (SLNs). Methodology: In the current study, various SLN formulations were developed using a central composite design (CCD) module using Design Expert-11 software. A modified solvent injection technique was used to prepare Saxagliptin nanoparticles coated with Eudragit RS100. The CCD was used to determine the independent variables and their effect on dependent variables at varied levels. Evaluation studies such as particle size analysis, Zeta potential, polydispersity index (PDI), drug loading, entrapment efficiency, in-vitro drug release studies, and in vivo pharmacokinetic studies were performed for the optimized SLN formulation. The reversed-phase HPLC method was developed and validated for the estimation of the pharmacokinetic parameters of the pure drug and prepared SLNs. Results: The effect of independent variables (A1: amount of lipid, A2: amount of polymer, A3: surfactant concentration, and A4: homogenization speed) on dependent variables (R1: particle size, and R2: entrapment efficiency) was established in great detail. Observed responses of the prepared and optimized Saxagliptin SLN were close to the predicted values by the CCD. The prepared SLNs depicted particle sizes in the range of 212–442 nm. The particle size analysis results showed that an increase in the lipid concentration led to an increase in particle size. The developed bioanalytical method was noted to be very specific and robust. The method accuracy varied from 99.16% to 101.95% for intraday, and 96.08% to 103.12% for inter day operation at low (5 mcg/mL), moderate (10 mcg/mL), and higher (15 mcg/mL) drug concentrations. The observed Zeta potential values for the prepared SLNs were in the range of −41.09 ± 0.11 to 30.86 ± 0.63 mV suggesting quite good stability of the SLNs without any aggregation. Moreover, the polydispersity indices were in the range of 0.26 ± 0.051 to 0.45 ± 0.017, indicative of uniformity of sizes among the prepared SLNs. In vivo study outcomes proved that Saxagliptin oral bioavailability significantly enhanced in male Albino Wistar Rats via SLN formulation and Eudragit RS100 coating approach. Conclusions: The developed and optimized Saxagliptin SLNs revealed enhanced Saxagliptin bioavailability in comparison to the native drug. Thus, this formulation strategy can be of great importance and can be implied as a promising approach to enhance the Saxagliptin bioavailability for facilitated T2DM therapy.

Eluxadoline-Loaded Eudragit Nanoparticles for Irritable Bowel Syndrome with Diarrhea: Formulation, Optimization Using Box–Behnken Design, and Anti-Diarrheal Activity

“…The pure ELD showed prominent functional group peaks at 3117 cm −1 (-NH- str), 3117 cm −1 (-NH-), 1696 cm −1 (-COOH), 1658 cm −1 (-RCONH2-), and 1429 cm −1 (-C=C-), which confirmed the purity of the drug [ 47 ]. The peaks at 3532 cm −1 and 3239 cm −1 (CH aliphatic stretching) were visible in the spectra of eudragit RS100 [ 48 ]. The characteristic absorption bands of ELD diminished or disappeared in the fingerprint region of the drug, which indicated that the drug encapsulated inside the eudragit polymer, and the appearance of new peaks in the ENP2 corresponding eudragit and PVA confirmed successful entrapment.…”

Development, Optimization and in Vitro Characterization of Haloperidol Nanocrystals Using 32 Factorial Design

“…The pellet was kept in a sample holder and scanned from 4000 cm -1 to 400 cm -1 in an FT-IR spectrophotometer. The possible interaction between Haloperidol PVP K30 and Poloxamer 407 was assessed by comparing FT-IR spectra of the pure drug (Haloperidol), polymer (PVP K30) and surfactant (poloxamer 407) [26,27].…”