Metformin Hydrochloride Loaded Mucoadhesive Microspheres and Nanoparticles for Anti-Hyperglycemic and Anticancer Effects Using Factorial Experimental Design.

Background: Metformin hydrochloride (HCl) microspheres and nanoparticles were formulated to enhance bioavailability and minimize side effects through sustained action and optimized drug-release characteristics. Initially, the same formulation design with different ratios of metformin HCl and Eudragit RSPO was used to formulate four batches of microspheres and nanoparticles using solvent evaporation and nanoprecipitation methods, respectively. Methods: The produced formulations were evaluated based on particle size and shape (particle size distribution (PSD), scanning electron microscope (SEM)), incompatibility (differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR)), drug release pattern, permeation behavior, in vivo hypoglycemic effects, and in vitro anticancer potential. Results: Compatibility studies concluded that there was minimal interaction between metformin HCl and the polymer, whereas SEM images revealed smoother, more spherical nanoparticles than microspheres. Drug release from the formulations was primarily controlled by the non-Fickian diffusion process, except for A1 and A4 by Fickian, and B3 by Super case II. Korsmeyer-Peppas was the best-fit model for the maximum formulations. The best formulations of microspheres and nanoparticles, based on greater drug release, drug entrapment, and compatibility characteristics, were attributed to the study of drug permeation by non-everted intestinal sacs, in vivo anti-hyperglycemic activity, and in vitro anticancer activity. Conclusion: This study suggests that the proposed metformin HCl formulation can dramatically reduce hyperglycemic conditions and may also have anticancer potential.

Surface Deposition and Coalescence and Coacervation Phase Separation Methods: In Vitro Study and Compatibility Analysis of Eudragit RS30D, Eudragit RL30D, and Carbopol-PLA Loaded Metronidazole Microspheres.

Metronidazole (MTZ) has extremely broad spectrum of protozoal and antimicrobial activity and is clinically effective in trichomoniasis, amoebic colitis, and giardiasis. This study was performed to formulate and evaluate the MTZ loaded microspheres by coacervation phase separation and surface deposition and coalescence methods using different polymers like Gelatin, Carbopol 934P, Polylactic Acid (PLA), Eudragit RS30D, and Eudragit RL30D to acquire sustained release of drug. In vitro dissolution studies were carried out in phosphate buffer (pH 7.4) for 8 hours according to USP paddle method. The maximum and minimum release of MTZ from microspheres observed were 84.81% and 76.6% for coacervation and 95.07% and 80.07% for surface deposition method, respectively, after 8 hours. Release kinetics was studied in different mathematical release models. The SEM and FTIR studies confirm good spheres and smooth surface as well as interaction between drug and polymers. Though release kinetic is uncertain, the best fit was obtained with the Korsmeyer kinetic model with release exponent (n) lying between 0.45 and 0.89. In vitro studies showed that MTZ microspheres with different polymers might be a good candidate as sustained drug delivery system to treat bacterial infections.

Characterization and Compatibility Studies of Different Rate Retardant Polymer Loaded Microspheres by Solvent Evaporation Technique: In Vitro-In Vivo Study of Vildagliptin as a Model Drug.

The present study has been performed to microencapsulate the antidiabetic drug of Vildagliptin to get sustained release of drug. The attempt of this study was to formulate and evaluate the Vildagliptin loaded microspheres by emulsion solvent evaporation technique using different polymers like Eudragit RL100, Eudragit RS100, Ethyl cellulose, and Methocel K100M. In vitro dissolution studies were carried out in 0.1 N HCl for 8 hours according to USP paddle method. The maximum and minimum drug release were observed as 92.5% and 68.5% from microspheres, respectively, after 8 hours. Release kinetics were studied in different mathematical release models to find out the linear relationship and release rate of drug. The SEM, DSC, and FTIR studies have been done to confirm good spheres and smooth surface as well as interaction along with drug and polymer. In this experiment, it is difficult to explain the exact mechanism of drug release. But the drug might be released by both diffusion and erosion as the correlation coefficient (R (2)) best fitted with Korsmeyer model and release exponent (n) was 0.45-0.89. At last it can be concluded that all in vitro and in vivo experiments exhibited promising result to treat type II diabetes mellitus with Vildagliptin microspheres.

Design, characterization and in-vitro evaluation of different cellulosic acrylic and methacrylic polymers loaded aceclofenac microspheres.

The aspire of this attempt was to design and evaluate aceclofenac loaded sustained release microspheres by emulsion solvent evaporation method, using different polymers like Ethyl cellulose (EC), Kollidon SR (KSR), Eudragit RS 100, Eudragit RL 100 and Hydroxypropylmethyl Cellulose (HPMC K100M). Microspheres were prepared using different stirring rate (1200, 1500, 2000rpm) and larger microspheres were obtained with lower stirring rate. Performance of microspheres was evaluated in terms of in vitro dissolution study which was allowed according to USP paddle method using Phosphate Buffer (pH 6.8) for 8 hours. UV-spectrophotometric method was used to calculate the drug content and the maximum and minimum release of aceclofenac from microspheres was observed 96.08% and 46.41% for formulation F18 and F5 after 8 hours respectively. Dissolution data were fitted by different mathematical models such as the zero order plot, first order plot, Higuchi plot, Hixon-Crowel plot and korsemeyer plot. Korsemeyer model has found to best fitted with release data. Scanning electron microscopic technique was performed to obtain the particle size and morphological changes due to different polymers. Fourier Transform Infra-red (FT-IR) spectroscopy was performed to find out any interaction of drug with the polymers. The drug might be released by both diffusion and erosion as data were best fitted with Korsemeyer model. So it has been demonstrated that aceclofenac microspheres containing different cellulosic, acrylic and methacrylic loaded polymers may be excellent candidates for consideration in drug delivery systems.

In vitro study on tamsulosin release kinetics from biodegradable PLGA in situ implants.

The objective of this study was to evaluate the effect of drug loading and the effect of excipients on the release pattern of tamsulosin tydrochloride from in situ PLGA implants formed in vitro in gelatin gel. This system is prepared by dissolving a biodegradable polymer (DL-PLGA 70K) in biocompatible solvent, dimethyl sulfoxide (DMSO). Then either the drug or drug with excipients was added to it. The drug solution was poured into the hollow of gelatin gel, the solvent dissipated into the surrounding gelatin base through diffusion leading phase separation and subsequent coagulation of the polymer. The drug formed a rod like implant in situ. Two types of implants were prepared such as implants containing tamsulosin hydrochloride and implants containing tamsulosin hydrochloride with biocompatible excipients such as Tween 20, Tween 60, Span 20, Span 80, Chremophore EL, or Chremophore RH 40. In vitro dissolution studies were performed in static condition using phosphate buffer (pH 7.4) to observe the release of drugs from these implants for 10 days. Formulation containing only tamsulosin hydrochloride showed that drug loading was 83.54%, 90.23%, 86.72%, 89.17% and 94.08% against the actual drug content of 9.09%, 13.04%, 16.67%, 20% and 23.08% respectively. The release rate of drug was 64.51%, 70.64%, 74.08%, 76.12% and 80.05% accordingly. It can be concluded that the release rate of drug increases with increasing drug concentrations. The other formulation containing tamsulosin with excipients showed that the release rate was 74.70%, 75.14%, 60.03%, 63.83%, 70.82% and 76.43% against same conc. of drug (8.7% of drug) but different excipients such as tween 20, tween 60, span 20, span 80, chremophore EL and chremophore RH 40 respectively. The loading efficiency was 79.33%, 87.34%, 91.91%, 94.19%, 88.48% and 95.34% respectively. It can be concluded that excipient lowers the release rate of the drug and may prolong the activity and overall release kinetics.