International Journal of Pharmaceutical Sciences and Drug Research

1-10

Authors: Pranavkumar Shah*, Bhavin Dhadhuk

The liquid chromatography mass spectrometry (LC-MS) compatible, stability-indicating, specific, linear, accurate, sensitive with less run-time related impurities reversed phase high-performance liquid chromatography (RP-HPLC) related impurities method has been developed for olmesartan medoxomil (OLM), chlorthalidone (CHLR), and cilnidipine (CIL) drug combinations, and the method has been validated according to ICH and US-FDA guidelines. The chromatographic separation was performed by using Hypersil-BDS Thermo-Scientific, C18 (12.5 cm, 4.6 mm, 5 microns particle size) column. Mobile phase-A was prepared by mixing 3.85 gm ammonium acetate in HPLC water and adjust pH 5.0 by using diluted acetic acid. Acetonitrile was taken as mobile phase-B. Initial mobile phase ratio (55:45 v/v) was adjusted for mobile phase-A: mobile phase-B followed by gradient program. Other chromatographic conditions such as column temperature 25 degrees, flow rate 1.0 mL/minutes with the detection wavelength at 260 nm. The retention time for CHLR impurity A, olmesartan (OL), OLM impurity A, were found about 2.7, 3.3, and 7.2 minutes respectively, with a total run time of 18.0 minutes. The linearity calibration plot was performed and found linear relationship over the concentration range of 1.25 limit of quantitation (LoQ)–18.75 μg/mL, 3.6 LoQ–60.0 μg/mL, 3.6 LoQ– 60.0 μg/mL respectively for CHLR impurity A, OL and OLM impurity A respectively. The limit of detection (LoD) and LoQ were found 0.4 ppm (μg/mL) and 1.2 ppm (μg/mL), 1.2 ppm (μg/mL) and 3.5 ppm (μg/mL), 1.1 ppm (μg/mL) and 3.3 ppm (μg/mL) for CHLR impurity A, OL and OLM impurity A respectively. The accuracy was determined by recovery studies and was found between 90.0–110.0%. The developed analytical method has been validated for LoD-LoQ, specificity, linearity, accuracy, precision, robustness, and ruggedness, which were well within the acceptance limit as per ICH guidelines. All the degradation products generated by stress conditions were found to be well separated from one another (all drug components and impurities). The developed method with shorter runtime was successfully implemented for routine quality control and stability analysis to check the quality of OLM, CHLR, and CIL drug combinations.

17-21

Authors: K. Kumar*, Sobhna Singh

This study was performed with the objective of developing and validating a UV-spectroscopic method for estimating contents of prulifloxacin in simulated intestinal fluid (SIF), i.e., phosphate-buffer media with a pH of 6.8 as per ICH guidelines. The λmax for prulifloxacin in phosphate-buffer media pH 6.8 was found to be 272 nanometers. The calibration curve of the drug followed linearity in-between 1–9 μg/mL concentration range, and the correlation coefficient value was found equal to 0.9995. We tested this proposed method onto the bulk and marketed pharmaceutical formulation (tablets) also to find out the contents of drugs. Using a developed method for estimation of prulifloxacin in simulated intestinal fluid (SIF), the drug was found to be in-between 101.91 and 104.02% in marketed tablets, which shows a good agreement with that of the claimed level. Accuracy of the developed method was established through recovery experimentation, performed for three spiked percent concentrations-75, 100, and 125%. The percentage recovery was found to be in between 97.27 and 101.82%. Low values of percentage RSD supported accuracy as well as the reproducibility of a developed method. The precision of the developed method was established by good in-limit intraday and interday experimental variations and through repeatability tests. Values of % relative standard deviation (RSD) less than two confirmed the precision of a developed method. The ruggedness of the developed method was validated by performing drug estimation by two different performers. This proposed spectroscopic method has proved to be a rapid and successful method for routine analysis of prulifloxacin in simulated intestinal fluid.

29-34

Authors: Mayuri Jain1, Shailja Choudhary1, Mojahidul Islam2*

Ceftriaxone, a third-generation cephalosporin antibiotic, is an important antibiotic used in the treatment of invasive infections caused by certain bacteria such as the penicillin-resistant microorganisms like Staphyloccocus aureus, strains of S. pneumonia, S. aureus and Enterobacteriaceae, particularly among E. coli. There is increasing antimicrobial resistance of Ceftriaxone in particular against these strains of bacteria. . This study has been conducted to formulate, evaluate and optimize chitosan-coated ceftriaxone loaded microparticles with better efficacy and also observes the minimum inhibitory concentration (MIC) against strains of bacteria. Emulsion crosslinking method was used for the formulation of microparticles of ceftriaxone by using chitosan as a polymer and glutaraldehyde as a crosslinking agent which is optimized by using Box-Behnken design. Three independent variables were taken; effect of drug and the polymer ratio, effect of the stirring speed and effect of crosslinking agent and dependent variables were microparticles entrapment efficiency and the in vitro drug release. Following optimization of the formulations, physical characterization as well as entrapment efficiency and ultimately in-vitro evaluation was performed. Physical characterization include optical microscopy, scanning electron microscope (SEM) and dynamic light scattering (DLS) to check there physical properties. The method used for the formulation of microparticle had the optimum entrapment efficiency of 61.7% which was increase with the increase in the addition of the more amount of chitosan and glutaraldehyde and method also achieved the good in vitro release. MIC studies of microparticles were done against Klebsiella pneumonia, Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and it was found that the formulations showed decrease in MIC.

40-45

Authors: Shailja Choudhary1, Mayuri Jain1, Mojahidul Islam2*

Curcumin being component of Curcuma longa is a natural polyphenol, observing on a chemical level, curcumin is a natural polyphenol which is denominated (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene3,5-dione) which is usually extracted through the rhizomes of Curcuma longa. Structurally, it is composed of a trio of chemical identities on a molecular level: dual aromatic ring system. The objective of the research was to design, development, and characterization of herbal drug-loaded albumin nanoparticles to cure Parkinson’s disease for improving and increasing the therapeutic efficacy and also reducing the frequency of dose. The optimized formulations were obtained after applying the design of the experiment, which was the Box Behnken method, where three independent variables, polymer concentration, stirring time, and crosslinker concentration, were selected. Curcumin nanoparticles loaded with albumin were formulated by the ph coacervation method in which ethanol was used as a desolvating agent along with a cross-linking agent (Glutaraldehyde) and albumin as the polymer. The particle size and polydispersity index of curcumin loaded albumin nanoparticles was measured via a dynamic light scattering technique. Drug release research conducted using the in vitro method over the duration of 24 hours. Ex vivo drug release study of the albumin nanoparticles was performed using a nasal membrane of a goat. It has been shown that in case of hydrophilic matrices, swelling of the polymer occurs followed by the release of drug by diffusion which was best explained by Korsmeyer-Peppas equation, which indicates drug release through diffusion which occurs by swelling of a polymer matrix and remained constant throughout the release of drug in the body. By virtue of particle size, the designed nanoparticles effortlessly go into the nasal mucosa.

53-57

Authors: Ishfaq S. Khan1*, Khalid Bashir2, Naveed Gulzar1, Yaseen M. Bhat3

The present study was conducted to evaluate the mutagenic and antimutagenic potential of Cousinia thomsonii (CT) extract in bone marrow cells of male wistar rats using some important parameters like micronucleated polychromatic erythrocyte (MnPCE), mitotic index (MI), chromosomal aberrations (CA), and polychromatic erythrocyte (PCE) to normochromatic erythrocyte ratio (PCE/NCE). Thirty male rats of Wistar strain were divided into 6 groups with 5 rats in each group. Group 1 rats were taken as negative control having free access to distilled water and rat feed. Group 2 rats were taken as positive control treated with mutagen cyclophosphamide (CP) at a dose of 60 mg/kg b wt. for 2 days. Group 3 and 4 were treated with CT extract at dose of 100 and 200 mg/kg b wt. for 20 days. Group 5 and 6 were treated with 100 and 200 mg/kg b wt of CT extract for the first 18 days and the last 2 days with CP at dose concentration of 60 mg/kg. It was found that rats treated with CT extract alone did not produce any significant changes in MnPCE, PCE/NCE ratio, CA, and MI when compared with control-treated rats (group 1). However, in group 5 and 6 rats treated with CT extract in combination with CP, a protective effect was observed against cyclophosphamide-induced cellular mutagenicity. In concluding remark, CT was found to show antigenotoxic potential and also produce protective antimutagenic effects against CP induced chromosomal damage.

65-72

Authors: Vipulbhai Mandli1*, Shailesh T. Prajapati2

The purpose of this research was to prepare and evaluate monolithic drug-in-adhesive type patches of rasagiline mesylate (RM) containing penetration enhancer and having 7-day wear property. Preformulation studies like solubility in permeation enhancers, compatibility study, transmission study, uptake study, and crystallization study of RM in various pressure-sensitive adhesive (PSA) polymers were performed. The transdermal system was prepared by the solvent casting method. The effects of various permeation enhancers (Propylene glycol, oleic acid, isopropyl palmitate, and lauryl lactate) on the ex-vivo transcutaneous absorption of RM through human cadaver skin were evaluated by modified Franz diffusion cell system. Ex-vivo transcutaneous absorption of the prepared transdermal patch was performed using different concentrations of Lauryl lactate (3, 5, and 7%). In-vitro Adhesion testing (Peel, tack shear, etc.) was performed on different dry grams per square meter (GSM) of patches like 80GSM, 100 GSM, and 150 GSM. The final transdermal patches were tested for appearance, the weight of matrix, thickness, % assay of drug content, in-vitro adhesion testing, cold flow study, and ex-vivo skin permeation studies. Based on crystallization study and adhesion testing, Durotak-4098 (14% drug concentration) was selected as a PSA. A patch containing Lauryl lactate showed the highest cumulative permeation compared to other permeation enhancers. The patch containing 5% lactate showed greater transdermal flux (2.36 μg/cm2/hr). Patch with 150 dry GSM showing promising adhesion properties. Backing film Scotchpak 9723 and release liner Saint Gobain 8310 was selected based on transmission and uptake study of RM. The stability study indicates that developed formulation remains stable. In conclusion, the present research confirms the practicability of developing a RM transdermal system.

80-86

Authors: Abhishek Biswal R, Riyaz Sharif S, Vivek Pazhamalai*

Delivering a potential drug is a predominant challenge in medicinal chemistry. In this study, bio-organic compounds of Cymbopogon citratus was screened by analysing physiochemical properties like solubility, permeability, efficacy, toxicity, and metabolic stability. The optimization of drug potential against virulent protein was calculated by using docking algorithm Autodock 4.2.3. Structure-based ligand docking reveals that the compounds had better inhibition potential against virulent enzymes with insoluble and impermeable activities. The organic compounds of Cymbopogon citratus were screened using Lipinski rule of five and absorption, distribution, metabolism, excretion/toxicity (ADME/T) prediction for drug likeliness. The structure-based ligand docking was done between bioactive compounds of plant and virulent protein that cause diseases. The interaction was visualized using Discovery studio and were studies. The molecular docking of bioactive compounds resulted in better inhibition potential with controlled lipophilicity level, without causing toxicity that harms the natural habitat of humans. The compounds, 1,3,4-trimethyl -3cyclohexene-1-carboxaldehyde, exhibit binding energy -4.70 Kcal/mol followed by β-myrcene –4.35 Kcal/mol and Geraniol –4.35 Kcal/mol. Hence, structure-based ligand docking and in silico ADME/T studies revealed that the compounds have better inhibition potential against Apolipoprotein by improving the prediction of drug compounds.