Chhaganbhai N. Patel

Effect of crosslinker concentration on characteristics of superporous hydrogel.

Aim: Synthesis of superporous hydrogel with different concentrations of crosslinker was carried out using solution polymerization to study its effect on characteristics of superporous hydrogel. Methylene-bis-acrylamide was used as a crosslinker. Materials and Methods: The characterization studies were performed by measurement of apparent density, porosity, swelling studies, mechanical strength studies, and scanning electron microscopy analysis. Results and Discussion: As the concentration of crosslinker increased from 7.37% to 14.36 % the porosities decreased. In double distilled water, superporous hydrogels showed good increase in equilibrium swelling capacity compared to that in simulated gastric fluid. Scanning electron microscopic images clearly indicated the formation of interconnected pore and capillary channels. Characterization studies revealed that the increase in crosslinker concentration is beneficial from the mechanical stability point of view, but at the same time the decrease in porosity may lead to decrease in drug release rate by diffusion through these capillary channels. Batches B1 and B2 with low concentrations of crosslinker provide good porous structure, swelling characteristics, and mechanical strength appropriate for further applications of superporous hydrogel-based drug delivery systems. Conclusion: The concentration of crosslinker affects the porous structure, swelling characteristics and mechanical strength. By setting appropriate degree of crosslinking it is possible to prepare superporous hydrogel having desired characteristics, which will provide a platform to design the drug delivery systems based on it.

Preparation and Characterization of Self-Microemulsifying Drug Delivery System of Olmesartan Medoxomil for Bioavailability Improvement.

Olmesartan medoxomil (OLM) is an angiotensin II receptor blocker (ARB) antihypertensive agent administered orally that has absolute bioavailability of only 26% due to the poor aqueous solubility (7.75 μg/ml). The aim of the present investigation was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral absorption of OLM. The solubility of OLM in various oils, surfactants, and cosurfactants was determined. Pseudoternary phase diagrams were constructed using Acrysol EL 135, Tween 80, Transcutol P, and distilled water to identify the efficient self-microemulsification region. Prepared SMEDDS was further evaluated for its emulsification time, drug content, optical clarity, droplet size, zeta potential, in vitro dissolution, and in vitro and ex vivo drug diffusion study. The optimized formulation S2 contained OLM (20 mg), Tween 80 (33%v/v), Transcutol P (33%v/v), and Acrysol EL 135 (34%v/v) had shown the smallest particle size, maximum solubility, less emulsification time, good optical clarity, and in vitro release. The in vitro and ex vivo diffusion rate of the drug from the SMEDDS was significantly higher than that of the plain drug suspension. It was concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route.

Formulation and Evaluation of Liquisolid Compacts for Olmesartan Medoxomil

Olmesartan medoxomil is an angiotensin type II receptor blocker, antihypertensive agent, administered orally. It is highly lipophilic (log P 5.5) and a poorly water-soluble drug with absolute bioavailability of 26%. The poor dissolution rate of water-insoluble drugs is still a major problem confronting the pharmaceutical industry. The objective of the present investigation was to develop liquisolid compacts for olmesartan medoxomil to improve the dissolution rate. Liquisolid compacts were prepared using Acrysol El 135 as a solvent, Avicel PH 102, Fujicalin and Neusilin as carrier materials, and Aerosil as coating material in different ratios. The interaction between drug and excipients was characterized by DSC and FT-IR studies, which showed that there is no interaction between drug and excipients. The powder characteristics were evaluated by different flow parameters to comply with pharmacopoeial limits. The dissolution studies for liquisolid compacts and conventional formulations were carried out, and it was found that liquisolid compacts with 80% w/w of Acrysol EL 135 to the drug showed significant higher drug release rates than conventional tablets. Amongst carriers used Fujicalin and Neusilin were found to be more effective carrier materials for liquid adsorption.

RP-HPLC method for simultaneous estimation of tenofovir disoproxil fumarate, lamivudine, and efavirenz in combined tablet dosage form

Background: A simple, precise, accurate, and rapid reverse phase-high performance liquid chromatography (RP-HPLC) method with UV-Visible detector has been developed and subsequently validated for the simultaneous determination of tenofovir disoproxil fumarate (TDF), lamivudine (LAMI), and efavirenz (EFV) in their combined tablet dosage form. Materials and Methods: The separation was based on the use of a Kromasil C18 analytical column (150 × 4.6 mm, i.d., 5 μm). The mobile phase consisted of a mixture of 70 volumes of methanol and 30 volumes of 10 mM phosphate buffer (pH 5.0). The separation was carried out at 40°C temperature with a flow rate of 1 ml/min. Results: Quantitation was achieved with UV detection at 254 nm, with linear calibration curves at concentration ranges of 1–6 μg/ml for TDF and LAMI and 2–12 μg/ml for EFV. The recoveries obtained were 99.46–101.36% for LAMI, 99.57–101.42% for TDF, and 99.96–100.87 for EFV. Conclusion: The method was validated according to International conference of harmonisation guidelines in terms of accuracy, precision, specificity, robustness, limits of detection and quantitation, and other aspects of analytical validation.

Reversed phase-high performance liquid chromatographic method for simultaneous estimation of tolperisone hydrochloride and etodolac in a combined fixed dose oral formulations

A reversed-phase liquid chromatographic (RP-HPLC) method was developed for the simultaneous determination of tolperisone hydrochloride (TOLP) and etodolac (ETD) in a combined fixed dose oral formulation. The analysis was carried out using a phenomenax C-18, pre-packed column. A mobile phase containing a phosphate buffer (pH 5.5) : Methanol : Acetonitrile : Tri-ethylamine (40 : 40 : 20 : 1.5), with the pH adjusted to orthophosphoric acid, was pumped at a flow rate of 1.0 ml min1 with a UV-detector and PDA detection at 257 nm. Retention time was 3.91 minutes and 6.89 minutes for TOLP and ETD, respectively. The method was validated for linearity, accuracy, precision, sensitivity, and specificity. The method showed good linearity in the range of 3 – 21 μg ml for TOLP μg / ml and 8 – 56 μg / ml for ETD. The detection limit of the proposed method was 0.16 μg / ml and 0.58 μg / ml for TOLP and ETD, respectively. The quantification limit of the proposed method was 0.51 μg / ml and 1.7 μg / ml for TOLP and ETD, respectively. The % recovery was within the range of 99.42 – 101.15 for TOLP and 98.63 – 100.94 for ETD. The percentage RSD for precision of the method was found to be less than 2%. The method was validated as per the International Conference on Harmonization (ICH) guidelines. The developed method could be applied for routine analysis of TOLP and ETD in tablet dosage form.

Preparation and evaluation of sublingual tablets of zolmitriptan

Aim: Zolmitriptan is a 5-HT receptor agonist (1B/1D). It is used in the acute treatment of migraine having low bioavailability about 40% orally due to hepatic first pass metabolism. The purpose of the present research was to formulate fast acting sublingual tablets of zolmitriptan. Materials and Methods: Sublingual tablets were prepared using ispaghula husk powder, gellan gum, sodium alginate as super disintegrating polymers and citric acid, tartaric acid and camphor as permeation enhancers by direct compressible technique and evaluated for weight variation, thickness, friability, content uniformity, hardness, disintegration time, wetting time, in-vitro drug release, in-vitro and ex-vivo permeation study. Stability study of optimized formulation was performed as per ICH (International Conference on Harmonisation) guideline. Results: The in-vitro disintegration time of the optimized formulation (D5) was 9 ± 2 s and all formulations showed 100% of dissolution within 6 ± 2 min. Formulation containing 4% of gellan gum (D5) showed highest disintegration and 2% of citric acid formulation (P3) showed highest permeation 88% within 30 min and ex-vivo permeation was 52% within 30 min. Optimized formulation was stable for 1 month during stability study as per ICH guideline. Conclusion: The sublingual tablet formulation gives better results using natural super disintegrant for fast onset of action.

A simple and sensitive HPTLC method for simultaneous analysis of tolperisone hydrochloride and etodolac in combined fixed-dose oral solid formulation

Tolperisone hydrochloride (TOLP; (R,S)-2-methyl-1-(4methylphenyl)-3piperidine-1-yl propan-1-one monohydrochloride; Figure 1) is used as a centrally acting muscle relaxant in several acute and chronic spastic conditions and arthritis [1, 2]. Etodolac (ETD; (R,S)-2[1,8-diethyl-4,9-dihydro-3H-pyrano (3,4-b)indol-1-yl]acetic acid; Figure 2) is a nonsteroidal antiinflammatory drug [3]. The combination of these drugs (150 mg TOLP and 400 mg ETD) has been recently approved for the treatment of acute inflammation condition associated with spasm. Etodolac helps to relieve the pain from inflammation during spasm, when treated by tolperisone.

A validated stability-indicating HPTLC method for the estimation of gemcitabine HCl in its dosage form

Gemcitabine belongs to a class of drugs known as antimetabolites (pyrimidine analog) used in various carcinomas, such as pancreatic cancer, bladder cancer, and breast cancer. The present study deals with the development and validation of a stability-indicating highperformance thin-layer chromatography (HPTLC) method for the estimation of gemcitabine using TLC plates precoated with silica gel 60 F254 as stationary phase and toluene-methanol-chloroform in the ratio of 3.6:3.6:3 (v/v/v) as the mobile phase. Gemcitabine (RF 0.48 ± 0.03) and its degradation products were well resolved. The wavelength selected for quantitation was 268 nm. The method was linear in the concentration range 500–3000 ng/band with a correlation coefficient of 0.997. The repeatability for six samples was 1.88%RSD. The intraday and interday precisions were 1.35–1.60%RSD and 1.57–1.81%RSD, respectively. The accuracy (recovery) was found to be in the range 98.30–101.75%. The drug was subjected to stress conditions such as hydrolysis, oxidation, photolysis, and heat. Degradation products produced as a result of the stress conditions did not interfere with the detection of gemcitabine; therefore the proposed method can be considered stability-indicating. Gemcitabine did not degrade under thermal and photolytic conditions but showed degradation under hydrolytic and oxidative conditions. The developed method was found to be simple, specific, precise, and stability-indicating.

Development and validation of the liquid chromatography-tandem mass spectrometry method for quantitative estimation of candesartan from human plasma

Introduction: A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for estimation of candesartan in human plasma using the protein precipitation technique. Materials and Methods: The chromatographic separation was performed on reverse phase using a Betasil C8 (100 × 2.1 mm) 5-μm column, mobile phase of methanol:ammonium tri-floro acetate buffer with formic acid (60:40 v/v) and flow rate of 0.45 ml/min. The protonated analyte was quantitated in positive ionization by multiple reaction monitoring with a mass spectrometer. The mass transitions m/z 441.2 → 263.2 and 260.2 → 116.1 were used to measure candesartan by using propranolol as an internal standard. Results: The linearity of the developed method was achieved in the range of 1.2–1030 ng/ml (r2 ≥ 0.9996) for candesartan. Conclusion: The developed method is simple, rapid, accurate, cost-effective and specific; hence, it can be applied for routine analysis in pharmaceutical industries.

Simultaneous analysis of eprosartan and hydrochlorothiazide in tablets by high-performance liquid chromatography.

Objective: A simple, precise and accurate isocratic reversed phase (RP) column high-performance liquid chromatographic (HPLC) method has been developed for simultaneous analysis of eprosartan (EPR) and hydrochlorothiazide (HCT) in tablet formulations. Materials and Methods: Isocratic RP-HPLC separation was achieved on phenomenex C18 column (250 × 4.6 mm i.d., 5 μm particle size) using mobile phase composed of 0.5% formic acid-methanol-acetonitrile [(80 : 25 : 20 v/v/v) pH, 2.80 ± 0.04] at a flow rate of 1.0 ml/min. The retention time for EPR and HCT was 7.69 ± 0.10 and 4.24 ± 0.09 minutes, respectively. The detection was performed at 272 nm. Results: The method was linear in the concentration range of 60-600 μg/ml for EPR and 2.5-25 μg/ml for HCT with a correlation coefficient of 0.9992 and 0.9997, respectively. The repeatability for six samples was 0.53 and 0.61 % RSD for EPR and HCT, respectively. The accuracy (recovery) was found to be in the range of 99.46 to 100.61% for EPR and 99.06 to 100.93% for HCT, respectively. Conclusions: The method was validated and successfully used for determination of the drugs in tablets.