Synthesis And Characterization Of pH-Sensitive Polyelectrolyte Nanogels For Oral Delivery Of Bovine Serum Albumin And Insulin As Model Proteins

Peptide and protein are administered parentrally owing to their instability and insufficient bioavailability through oral route. Parenteral administration is associated with poor patient compliance due to pain and discomfort by multiple injections. Oral administration can be beneficial to improve patient compliance and physiologic response to peptide and protein (e.g. insulin). The aim of the present study was to synthesize pH sensitive polyelectrolyte methyl methacrylate/itaconic acid (MMA/IA) nanogels to be used as a carrier for oral delivery of model proteins (BSA and insulin)

In vitro evaluation of commercially available theophylline sustained release tablets in Pakistan

The dissolution behavior of five commercially available brands of sustained release theophylline tablets was studied in phosphate buffer solutions of pH 1.2, 4.5, 5.5, 6.0 and 7.5 at 37 °C using the USP dissolution apparatus II (paddle method). Drug concentration in the samples was determined spectrophotometrically at 272 nm. For predicting the release characteristics of theophylline from selected commercially available tablets the data obtained in the dissolution studies was fitted into various mathematic models defining kinetic parameters of drug release like zero-order rate equation, first-order rate equation, Hixen-crowell cube root law, Higuchi equation and Korsemeyer-Peppas model. Tablets were subjected to weight variation test, hardness, drug content and in vitro release studies. The present study revealed that drug release increases with the increase of pH of the dissolution medium and also varies from brand to brand. Among the five selected brands, B1 and B4 showed better pH dependency and drug release behaviour. It has been suggested that possible reasons for difference in dissolution or drug release behaviour are the difference in the manufacturing techniques and the quantity of hydrophobic excepients used by different manufacturers, which retard the penetration of dissolution medium and ultimately decreases availability of drug in the solution.Colegio de Farmacéuticos de la Provincia de Buenos Aire

In vitro evaluation of commercially available theophylline sustained release tablets in Pakistan

The dissolution behavior of five commercially available brands of sustained release theophylline tablets was studied in phosphate buffer solutions of pH 1.2, 4.5, 5.5, 6.0 and 7.5 at 37 °C using the USP dissolution apparatus II (paddle method). Drug concentration in the samples was determined spectrophotometrically at 272 nm. For predicting the release characteristics of theophylline from selected commercially available tablets the data obtained in the dissolution studies was fitted into various mathematic models defining kinetic parameters of drug release like zero-order rate equation, first-order rate equation, Hixen-crowell cube root law, Higuchi equation and Korsemeyer-Peppas model. Tablets were subjected to weight variation test, hardness, drug content and in vitro release studies. The present study revealed that drug release increases with the increase of pH of the dissolution medium and also varies from brand to brand. Among the five selected brands, B1 and B4 showed better pH dependency and drug release behaviour. It has been suggested that possible reasons for difference in dissolution or drug release behaviour are the difference in the manufacturing techniques and the quantity of hydrophobic excepients used by different manufacturers, which retard the penetration of dissolution medium and ultimately decreases availability of drug in the solution.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Quantification of carbon dioxide released from effervescent granules as a predictor of formulation quality using modified Chittick apparatus

Purpose: To develop a method for the measurement of carbon dioxide (CO2) released from effervescent formulations. Methods: Effervescent granules were prepared using sodium bicarbonate and citric acid by fusion and solvent-assisted granulation methods. The amount of CO2 released was determined from the maximum pressure of gas release, time profile of pressure gradient using modified Chittick apparatus and gravimetric changes following effervescence. Results: The amount of CO2 released from effervescent granules prepared by fusion method was 8.125, 8.763 and 7.98 mM/g measured by ideal gas equation, pressure gradient and gravimetric method, respectively. The formulation prepared by solvent-assisted granulation showed 5.525, 5.475 5.36 mM/g of carbon dioxide measured by the above three methods, respectively. The effervescent granules prepared by fusion method showed approximately 2 % loss in effervescence. However, approximately 39 % loss in effervescence was observed for the formulation prepared by solventassisted granulation. The commercial products showed a loss in effervescence in the range of 5 - 15%. Conclusion: Modified Chittick’s apparatus is a useful analytical tool for monitoring of the CO2 from effervescent granules as a function of method of preparation

Fabrication and Biological Assessment of Antidiabetic α-Mangostin Loaded Nanosponges: In Vitro, In Vivo, and In Silico Studies

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-29, pub-electronic 2021-11-01Publication status: PublishedFunder: King Saud University; Grant(s): RSP-2021/406Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic β-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively

Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: Characterization, lyophilization and in-vivo evaluation

Introduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally. Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE). Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, −16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, −16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups. Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug

Freeze-Dried Lopinavir-Loaded Nanostructured Lipid Carriers for Enhanced Cellular Uptake and Bioavailability: Statistical Optimization, in Vitro and in Vivo Evaluations

Nanostructured lipid carriers (NLCs) loaded with lopinavir (LPV) were prepared by the high-shear homogenization method. The LPV-NLCs formulations were freeze-dried using trehalose as a cryoprotectant. In vitro release studies in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8) showed a burst release. The optimized freeze-dried formulation (LPV-NLC-7-Tres) had a particle size (PS), polydispersity index (PdI), zeta potential (ZP) and % entrapment efficiency (%EE) of 286.8 ± 1.3 nm, 0.413 ± 0.017, −48.6 ± 0.89 mV and 88.31 ± 2.04%, respectively. The optimized formulation observed by transmission and scanning electron microscopes showed a spherical shape. Differential scanning calorimetry study revealed the absence of chemical interaction between the drug and lipids. In vitro cellular uptake study using Caco-2 cell line showed a higher LPV uptake from LPV-NLC-7-Tres formulation compared to the free LPV-suspension. The 6-month stability study showed a minimum rise of ~40 nm in PS, while no significant changes in PdI, ZP and drug content of the LPV-NLC-7-Tres formulation stored at 5 °C ± 3 °C. The bioavailability of LPV following oral administration of LPV-NLC-7-Tres in male Wistar rats was found 6.98-fold higher than the LPV-suspension. In conclusion, the nanostructure lipid carriers are potential carriers for improving the oral bioavailability of lopinavir

Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer