Performance Evaluation of Montelukast Pediatric Formulations: Part I—Age-Related In Vitro Conditions

This study aimed to explore the potential of biopharmaceutics in vitro tools to predict drug product performance in the pediatric population. Biorelevant dissolution set-ups were used to predict how age and medicine administration practices affect the in vitro dissolution of oral formulations of a poorly water-soluble compound, montelukast. Biorelevant age-appropriate dissolution studies of Singulair® (granules and chewable tablets) were conducted with the µDISS profiler™, USP 4 apparatus, USP 2 apparatus, and mini-paddle apparatus. Biorelevant simulating fluids representative of adult and pediatric conditions were used in the dissolution studies. The biorelevant dissolution conditions were appropriately selected (i.e. volumes, transit times, etc.) to mimic the gastrointestinal conditions of each of the subpopulations tested. Partial least squares regression (PLS-R) was performed to understand the impact of in vitro variables on the dissolution of montelukast. Montelukast dissolution was significantly affected by the in vitro hydrodynamics used to perform the dissolution tests (µDISS profiler™: positive effect); choice of simulation of gastric (negative effect) and/or intestinal conditions (positive effect) of the gastrointestinal tract; and simulation of prandial state (fasted state: negative effect, fed state: positive effect). Age-related biorelevant dissolution of Singulair® granules predicted the in vivo effect of the co-administration of the formulation with applesauce and formula in infants. This study demonstrates that age-appropriate biorelevant dissolution testing can be a valuable tool for the assessment of drug performance in the pediatric population. Graphical Abstract

Formulation Development and In-vitro Evaluation of Sustained Release Tablets of Metoprolol Succinate

Metoprolol succinate is a β1 selective antagonist used an anti-arrhythmic, antiagina, antihypertensive. sustained release tablet of metoprolol succinate were formulated using polymers. The half-life of drug is relatively 4-6 hours. The formulation of metoprolol succinate tablet were produced by direct compression or wet granulation method. The formulations were evaluated for thickness, hardness, weight variation, friability and dissolution, drug content all the physical characteristics of the formulated tablets were within acceptable limits. The dissolution studies of Metoprolol succinate sustained release tablets reflects USP specification NMT 25%by 1 hours, 20-40%by 4 hours,40-60%by 8 hours and more than 80% by 20 hrs.

Formulation and Evaluation of Fast Dissolving Tablet of Ondansetron by Utilizing Liquisolid Compact Technique

Ondansetron is an anti-emetic drug which is insoluble in water. The present study was aimed to formulate and evaluate oral fast dissolving tablet of Ondansetron by Utilizing Liquisolid Compact Technique. The tablets were prepared by direct compression method and characterized by UV, FTIR studies. Six formulations (F1-F6) of ondansetron were prepared and tablets were evaluated for weight variations, hardness, thickness, friability, disintegration time, drug content and In-vitro dissolution studies gave satisfactory result. TF6 was found to be the best and acceptable formulation whose drug content was about 99.17±0.05 and percentage (%) drug release 97.49±2.03 in 10 min, high as compare to other formulation and has low disintegration time 17±0.01 as compare to other formulation which indicates that drug is rapidly dissolved and available at the site of action.

Cocrystallization of Febuxostat with Pyridine Coformers: Crystal Structural and Physicochemical Properties Analysis

Drug cocrystals and salts have promising applications for modulating the physicochemical properties and solubility of pharmaceuticals. In this study, a cocrystal and two salts of febuxostat (FEB) with pyridine nitrogen coformers, including 4, 4′-bipyridine (BIP), 3-aminopyridine (3AP) and 4-hydroxypyridine (4HP), were designed to improve the solubility of FEB. The single-crystal structures were elucidated, and their physical and chemical properties were investigated by IR, PXRD, and DSC. In addition, drug-related properties, including the solubility and powder dissolution rate were assessed. The solubility and powder dissolution studies showed that the FEB-BIP cocrystal and FEB-3AP salt have superior dissolution compared to FEB.

Formulation and Evaluation of Metoprolol Controlled Release Formulations

Aim: The main perspective of the present research work was to prepare Metoprolol floating controlled release formulations. Methodology: After performing the characterization studies, Metoprolol tablets were prepared using various concentrations of poly ethylene oxide (PEO) WSR 303 (5% to 30%) by direct compression method. Formulations MP1 and MP6 were formulated using PEO WSR 303. Various pre and post compression parameters were evaluated. Dissolution studies were performed for the prepared tablets using dissolution medium of 0.1N hydrochloric acid. Results: Characterization studies like Fourier Transform Infra Red (FTIR) and Scanning Electron Microscopy (SEM) for Metoprolol, Polyethylene oxide WSR 303 and their combination were carried out, which revealed that there is no interaction between drug and polymer. The dissolution studies showed the controlled release pattern of Metoprolol up to 24h. The formulation MP5 prepared using 25% w/w of PEO WSR 303 showed maximum drug release of 98.22% at 24h. Similar drug release profile was observed for MP6 which was formulated using 30%w/w PEO WSR 303. These two formulations were further added with various concentrations of sodium bicarbonate (5% to 15%) and citric acid (2.5% to 10%) which enhanced floating of drug. Formulation MP8 containing 10% of sodium bicarbonate with 25% PEO WSR 303 showed less buoyancy lag time and prolonged drug release. Formulation MP15 showed very less buoyancy lag time of 4sec. Conclusion: Thus the prepared Metoprolol floating tablets showed prolonged drug release which could be a promising formulation for anti-hypertensive patients.

In-vitro Study and In-vivo Predictions of Valsartan and Amlodipine Capsules through Micro Tablets

Aim: The present research work was carried out to develop Valsartan and Amlodipine capsules using micro tablets and to evaluate the in-vitro drug release characteristics. The study was targeted to determine the systemic concentrations using in-vivo prediction. Study Design: The in vivo parameters along with the marketed Valsartan and Amlodipine product was predicted using WinNonlin® software external prediction method. Place and Duration of the Study: The present work was carried out at Pacific Academy of Higher Education and Research University, Udaipur between the duration of February-2019 to November-2019. Methodology: The dissolution studies were performed for test and reference products in 900ml Phosphate buffer (pH 6.8), and the USP Type II apparatus at 50 RPM with a sinker. The in vivo pharmacokinetic prediction was performed using WinNonlin® Software. A mechanistic oral absorption model was built in Phoenix® WinNonlin® 8.2 software (Certara, Princeton, NJ, 08540, USA). Results: The in-vitro dissolution studies were comparable between the test product and the reference product. The Similarity factor achieved was 61.7 and 84.8 for Amlodipine and Valsartan test product in comparison with the reference product. An average percent prediction error for Cmax and AUC for both Valsartan and Amlodipine achieved was less than 10% for all IVIVC models. Conclusion: The relatively low prediction errors for Cmax and AUC observed strongly suggest that the Valsartan and Amlodipine IVIVC models are valid. The average percent prediction error of less than 10% indicates that the correlation is predictive and allows the associated dissolution data to be used as a surrogate for bioavailability studies.

Particle Engineering and Spray Drying Process designing for Solubility Enhancement of Lopinavir

To improve the solubility enhancement of solid dispersion of Lopinavir by spray-drying by adding the Soluplus as polymer that is compatible with Lopinavir, was evaluated and the process used for preparation of Spray dried solid dispersion was validated and the 1:3 ratio used for preparation of solid dispersion. Dissolution tests were carried out on several spray dried solid dispersion of Lopinavir and physical mixture. The solid dispersion characterized by DSC, XRD, % Entrapment Efficiency, solubility study, drug content determination, practical yield, dissolution studies. Keyword: Lopinavir, Soluplus, Spray Drying Technique, Dissolution studies

Preparation and Evaluation of Captopril Oral Floating Controlled Release Formulations

Aim: Dosing frequency is a major hurdle in geriatrics with frequent drug administration. In such cases, oral controlled release floating formulations are helpful which causes reduction in dosing frequency and fluctuation of drug levels in plasma. The main aim of the current research was to prepare Captopril floating controlled release formulations in order to achieve extended gastric retention in the upper GIT. Methodology: Captopril tablets were prepared using different concentrations of poly ethylene oxide water soluble resin (PEO WSR) 303 (5% to 30%) by direct compression technique. Captopril formulations CSP1 and CSP6 were formulated using PEO WSR 303. Pre and post compression parameters were evaluated. Dissolution studies were performed for the prepared tablets using 0.1N hydrochloric acid as dissolution medium. Results: The dissolution studies showed controlled drug release up to 12h. The formulation CSP5 prepared using 25% w/w of PEO WSR 303 showed maximum drug release of 97.97% at 12h. Almost similar drug release profile was also observed for CSP6 which was prepared using 30%w/w PEO WSR 303. These two formulations were further added with various concentrations of sodium bicarbonate (5% to 15%) and citric acid (2.5% to 10%) which enhanced floating of drug in Gastro intestinal tract (GIT). Formulation CSP8 containing 10% of sodium bicarbonate with 25% PEO WSR 303 showed less buoyancy lag time and prolonged drug release. Formulation CSP15 showed very less buoyancy lag time of 5sec. Characterization studies like Fourier Transform Infra Red spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) were also carried out. Conclusion: The prepared Captopril floating tablets could be an alternative formulation for prolonged drug release.

Bioavailability Enhancement of Ritonavir by Solid Dispersion Technique

Ritonavir is an antiretroviral agent used in the treatment of HIV-infection. It is a BCS class IV drug having poor aqueous solubility leading to poor bioavailability. Bioavailability is the amount of drug that enters the systemic circulation. The bioavailability is affected by various factors like solubility, dissolution and stability. In order to improve bioavailability, many techniques like solid dispersions, nanoparticles, liposomes, encapsulation methods were present. The main aim of this study is to improve the bioavailability of ritonavir with the help of Polyvinyl Pyrrolidone (PVP) K-30 by using solid dispersion technique. Different formulations were made with varied concentrations of polymer. Characterization of solid dispersion was done by phase solubility, drug content, Fourier transformed infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and in-vitro dissolution studies. From phase solubility studies that apparent solubility constant was found to be 42.227M-1. The drug content of the binary system of ritonavir and PVP was found to be ranging from 99.17% to 103.06%. %. FT-IR studies revealed that there was no drastic change in the wave number indicating polymer compatibility with drug. In-vitro dissolution studies proved that there was an increase in drug release of ritonavir with incremental ratios of polymer and F5 formulation has shown almost 95% of drug release. Keywords: Bioavailability, Solid dispersion, Polyvinyl pyrrolidine, Solvent evaporation, Dissolution.