Kolapalli Venkata Ramana Murthy

Physicochemical characterization and dissolution properties of meloxicam-cyclodextrin binary systems.

The objective of the work is physicochemical characterization of meloxicam (ME)-cyclodextrin (CD) binary systems both in solution and solid states and to improve the dissolution properties of meloxicam via complexation with alpha-, beta- and gamma-cyclodextrins. Detection of inclusion complexation was done in solution state by means of phase solubility analysis, mass spectrometry and 1H nuclear magnetic resonance (NMR) studies, and in solid state using differential scanning calorimetry (DSC), powder X-ray diffractometry, and in vitro dissolution studies. Phase solubility, mass spectrometry and 1H NMR studies in solution state revealed 1:1M complexation of meloxicam with all CDs. A true inclusion of ME with gamma-CD at 1:1 and 1:2M in solid state was confirmed by DSC, powder XRD and scanning electron microscopy (SEM) studies. Dissolution properties of ME-CDs binary systems were superior when compared to pure ME.

Physicochemical characterization and dissolution properties of nimesulide-cyclodextrin binary systems

The objective of this work is physicochemical characterization of nimesulide-cyclodextrin binary systems both in solution and solid state and to improve the dissolution properties of nimesulide (N) via complexation with α-, β, and γ-cyclodextrins (CDs). Detection of inclusion complexation was done in solution by means of phase solubility analysis, mass spectrometry, and 1H nuclear magnetic resonance (1H-NMR) spectroscopic studies, and in solid state using differential scanning calorimetry (DSC), powder x-ray diffractometry (X-RD), scanning electron microscopy (SEM), and in vitro dissolution studies. Phase solubility, mass spectrometry and 1H-NMR studies in solution revealed 1∶1 M complexation of N with all CDs. A true inclusion of N with β-CD at 1∶2 M in solid state was confirmed by DSC, powder X-RD and SEM studies. Dissolution properties of N-CD binary systems were superior when compared to pure N.

In vivo evaluation of modified gum karaya as a carrier for improving the oral bioavailability of a poorly water-soluble drug, nimodipine

This work examines the influence of modified gum karaya (MGK) on the oral bioavailability of a poorly water-soluble drug, nimodipine (NM), in comparison with that of gum karaya (GK). A cogrinding method was selected to prepare mixtures of NM and GK or MGK in a 1:9 ratio (NM:GK/MGK). Differential scanning calorimetry (DSC), Fourier transmission infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), solubility studies, and in vitro release studies were performed to characterize the properties of the cogrinding mixtures. No drug-carrier interactions were found, as confirmed by DSC and FT-IR studies. The XRD study revealed that the crystallinity of NM was identical in both the cogrinding mixtures and was decreased when compared to that of physical mixtures or pure NM. The in vitro release rate of NM from both cogrinding mixtures was significantly higher than that of physical mixtures or pure NM. The in vivo study revealed that the bioavailability of NM from pure drug was significantly lower when compared to the cogrinding mixtures. The oral bioavailability was found to be NM powder < cogrinding mixtures of NM and GK < cogrinding mixtures of NM and MGK < NM solution. It can be inferred from the above results that MGK, an economical carrier, could be used for the dissolution enhancement of NM.

Tablet formulation studies on nimesulide and meloxicam-cyclodextrin binary systems.

The objective of this work was to develop tablet formulations of nimesulide-β-cyclodextrin (NI-β-CD) and meloxicam-γ-cyclodextrin (ME-γ-CD) binary systems. In the case of nimesulide, 3 types of binary systems—physical mixtures, kneaded systems, and coevaporated systems—were studied. In the case of meloxicam, 2 types of binary systems—physical mixtures and kneaded systems—were investigated. Both drug-CD binary systems were prepared at 1∶1 and 1∶2 molar ratio (1∶1M and 1∶2M) and used in formulation studies. The tablet formulations containing drug-CD binary systems prepared by the wet granulation and direct compression methods showed superior dissolution properties when compared with the formulations of the corresponding pure drug formulations. Overall, the dissolution properties of tablet formulations prepared by the direct compression method were superior to those of tablets prepared by the wet granulation method. Selected tablet formulations showed good stability with regard to drug content, disintegration time, hardness, and in vitro dissolution properties over 6 months at 40°C±2°C and 75% relative humidity.

Studies on Optimizing In Vitro Transdermal Permeation of Ondansetron Hydrochloride Using Nerodilol, Carvone, and Limonene as Penetration Enhancers

The present investigation was carried out to formulate a terpene-based hydroxypropyl cellulose (HPC) gel drug reservoir system for its optimal transdermal permeation of ondansetron hydrochloride. The HPC gel formulations containing ondansetron hydrochloride (3% w/w) and selected concentrations of either nerodilol (0% w/w, 1% w/w, 2% w/w, 3% w/w, and 4% w/w), carvone (0% w/w, 2% w/w, 4% w/w, 8% w/w, and 10% w/w), or limonene (0% w/w, 2% w/w, 3% w/w, and 4% w/w) were prepared and subjected to in vitro permeation of the drug across rat epidermis. All the 3 terpene enhancers increased the transdermal permeation of ondansetron hydrochloride. The optimal transdermal permeation was observed with 3% w/w of nerodilol (175.3 ± 3.1 μg/cm2.h), 8% w/w of carvone (87.4 ± 1.6 μg/cm2.h), or 3% w/w of limonene (181.9 ± 0.9 μg/cm2.h). The enhancement ratio (ER) in drug permeability with 3% w/w nerodilol, 8% w/w carvone, and 3% w/w limonene were 21.6, 10.8, and 22.5, respectively, when compared with that obtained without a terpene enhancer (control). However, there was 1.04-, 2.09-, and 2.17-fold increase in the optimal drug flux obtained with carvone, nerodilol, and limonene, respectively, when compared with the desired drug flux (84 μg/cm2.h). It was concluded that the HPC gel drug reservoir systems containing either 3% w/w nerodilol or 3% w/w limonene act as optimal formulations for use in the design of membrane-controlled transdermal therapeutic system (TTS) of ondansetron hydrochloride.

Investigation on in vitro dissolution rate enhancement of indomethacin by using a novel carrier sucrose fatty acid ester

Background and the purpose of the studyThe purpose of the present investigation was to characterize and evaluate solid dispersions (SD) of indomethacin by using a novel carrier sucrose fatty acid ester (SFE 1815) to increase its in vitro drug release and further formulating as a tablet.MethodsIndomethacin loaded SD were prepared by solvent evaporation and melt granulation technique using SFE 1815 as carrier in 1:0.25, 1:0.5 1:0.75 and 1:1 ratios of drug and carrier. Prepared SD and tablets were subjected to in vitro dissolution studies in 900 mL of pH 7.2 phosphate buffer using apparatus I at 100 rpm. The promising SD were further formulated as tablets using suitable diluent (DCL 21, Avicel PH 102 and pregelatinised starch) to attain the drug release similar to that of SD.. The obtained dissolution data was subjected to kinetic study by fitting the data into various model independent models like zero order, first order, Higuchi, Hixon-Crowell and Peppas equations. Drug and excipient compatibility studies were confirmed by fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and scanning electron microscopy.ResultsThe in vitro dissolution data exhibited superior release from formulation S6 with 1:0.5 drug and carrier ratio using solvent evaporation technique than other SDs prepared at different ratio using solvent evaporation and melt granulation technique. The in vitro drug release was also superior to that of the physical mixtures prepared at same ratio and also superior to SD prepared using common carriers like polyvinyl pyrollidone and PEG 4000 by solvent evaporation technique. Tablets (T8) prepared with DCL21 as diluent exhibited superior release than the other tablets. The tablet formulation (T8) followed first order release with Non-Fickian release.ConclusionSFE 1815 a novel third generation carrier can be used for the preparation of SD for the enhancement of in vitro drug release of indomethacin an insoluble drug belonging to BCS class II.

Chronotherapeutic Drug Delivery from Indomethacin Compression Coated Tablets for Early Morning Pain Associated Rheumatoid Arthritis

As the main intent of delivering maximum concentration of drug available from the dosage form, an oral compression coated tablet (CCT) was intended to develop with a predetermined lag time of 6 hrs before immediate release of drug to target circadian rhythms of rheumatoid arthritis. Solid dispersions are promising approach to enhance drug release, which later will be developed as core tablet formulation and compression coated with polyethylene oxide (PEO WSR 303). Solid dispersions were formulated with different ratio of drug and carrier (sucrose fatty acid esters 1811) using solvent evaporation and melt granulation technique, optimized solid dispersion was formulated as core tablet with different diluents. Optimized core tablet was compression coated with PEO WSR 303 along with a channeling agent (DCL 21, mannitol, HPMC 5 cps and starch 1500). Lag time before immediate release of drug was markedly dependent on weight ratios of polymer and channeling agent used, which ranged from 4 to 12 hrs. Optimized solid dispersion (S9) was used for formulating optimized core tablet formulation (C8). CCT (T8) prepared with core tablet (C8) along with mannitol provided a lag time of 6 hrs with minimum concentration of channeling agent used, which was also supported from the permeability study results. Incompatibility and characterization was confirmed from DSC, XRD, FTIR and SEM studies. Unaltered Cmax and AUC0-t but delayed Tmax following oral ingestion of optimized formulation (T8) to human volunteers indicated clear lag time before immediate release of drug, which is suitable for treating rheumatoid arthritis following circadian rhythm.

Design and evaluation of lornoxicam bilayered tablets for biphasic release

The objective of the present investigation was to develop bilayered tablets of lornoxicam to achieve biphasic release pattern. A bilayered tablet, consisting of an immediate and controlled release layer, was prepared by direct compression technique. The controlled release effect was achieved by using various hydrophilic natural, semi synthetic and synthetic controlled release polymers such as xanthan gum, hydroxypropyl methylcellulose (HPMC) and polyethylene oxide (PEO) to modulate the release of the drug. The in vitro drug release profiles showed the biphasic release behavior in which the immediate release (IR) layer containing the lornoxicam was released within 15 minutes, whereas the controlled release (CR) layer controlled the drug release for up to 24 h. All the bilayered tablets formulated have followed the zero order release with non-Fickian diffusion controlled release mechanism after the initial burst release. FTIR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 24 h from optimized formulations was observed. Based on the release kinetic parameters obtained, it can be concluded that xanthan gum polymer was suitable for providing a biphasic release of lornoxicam.

Factorial Design Studies and Biopharmaceutical Evaluation of Simvastatin Loaded Solid Lipid Nanoparticles for Improving the Oral Bioavailability

Statins are HMG-CoA reductase inhibitors, which lower the cholesterol level through reversible and competitive inhibition; they are involved in the biosynthesis of cholesterol and other sterols. Simvastatin exhibits poor oral bioavailability (<5%) and undergoes extensive microsomal metabolism by CYP enzymes. CYP3A4 is the major metabolizing enzyme that metabolizes lactone form of simvastatin and significantly lowers intestinal uptake. The hydrophobic properties of simvastatin prevent complete dissolution of the drug in the intestinal fluid which also contributes to its lower bioavailability. SLNs are alternative carrier system to polymeric nanoparticles. SLNs are in submicron size range (1–1000 nm). To overcome the hepatic first pass metabolism and to enhance the bioavailability, intestinal lymphatic transport of drugs can be exploited. In the present study, attempt has been made to prepare solid lipid nanoparticles of simvastatin to improve the bioavailability. SLNs of simvastatin were prepared with Trimyristin by hot homogenization followed by ultrasonication method. The SLNs were characterized for various physicochemical properties and analytical techniques like PXRD, DSC to study thermal nature and morphology of formulation and excipients. Promising results of the study indicated the applicability of simvastatin solid lipid nanoparticles as potential tools for improvement of bioavailability of poorly soluble drugs.