Rabia Ismail Yousuf

Once-daily tablet formulation and in vitro release evaluation of cefpodoxime using hydroxypropyl methylcellulose: a technical note.

Summary and ConclusionsDecreasing the dose frequency of cefpodoxime proxetil increases patient compliance; patients prefer to take the drug once daily. It also improves the rate of bacterial killing and hastens the cure from the indications, and therefore increases compliance. The hydrophilic matrix of HPMC controlled the cefpodoxime proxetil release effectively for 24 hours; hence, the formulation can be considered as a once-daily sustained-release tablet of cefpodoxime proxetil. The formulation showed acceptable pharmacotechnical properties and assay requirements. In vitro dissolution studies indicated a sustained-release pattern throughout 24 hours of the study that was comparable to the theoretical release profile. Drug release kinetics indicated that drug release was best explained by Higuchi’s equation, as these plots showed the highest linearity (r2=0.9734), but a close relationship was also noted with zero-order kinetics (r2=0.9708). Korsmeyer’s plots indicated ann value of 0.57, which was indicative of an anomalous diffusion mechanism or diffusion coupled with erosion; hence, the drug release was controlled by more than one process. Hixson-Crowell plots indicated a change in surface area and diameter of the tablets with the progressive dissolution of the matrix as a function of time.

In-vitro assessment of cytotoxicity of halloysite nanotubes against HepG2, HCT116 and human peripheral blood lymphocytes

Halloysite is a clay mineral with chemical similarity to kaolin, a pharmaceutical ingredient. It consists of mainly aluminosilicate nanotubular particles in the size range of ∼ 200-1000 nm. Many studies have tried to empirically explore this novel clay for its potential in drug delivery systems but no work has yet studied its cytotoxicity from the perspective of oral drug delivery system. In this study, the halloysite nanotubes (HNTs) were subjected to size distribution analyses, which reveal more than 50% of nanotubes in the size range of 500 nm and rest mainly in the sub micrometer range. HNTs were then evaluated for in-vitro cytotoxicity against HCT116 (colorectal carcinoma) and HepG2 (hepatocellular carcinoma) cells which represent the earliest entry point and the first accumulating organ, respectively, for nanoparticles en-route to systemic circulation after oral delivery. Moreover, HNTs were tested for their cytogenetic toxicity against human peripheral blood lymphocytes. Both these results collectively indicated that HNTs are generally safe at practical concentrations of excipients for oral dosage forms.

Development of enteric coated flurbiprofen tablets using Opadry/Acryl-Eze system--a technical note.

Tablet coating is perhaps one of the oldest pharmaceutical processes still in existence (1). It offers many benefits namely: improving the aesthetic qualities of the dosage form, masking unpleasant odour or taste, easing ingestion, improving product stability and modifying the release characteristics of the drug. It is widely used in enteric coating, controlled release system and osmotic pump systems (2). Enteric coated dosage forms are designed to resist the destructive action of the gastric fluid and to disintegrate in the higher pH environment of the intestinal fluid. Polymer for enteric coating can be applied to solid dosage forms (i.e. granules, pellets, or tablets) from aqueous solutions of alkali salts, or organic solvent solutions. The most commonly used pH-sensitive enteric coating polymers today include: cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropyl methyl cellulose phthalate (HPMCP) and methacrylic acid copolymers (3). In recent years, acrylic copolymers have evolved as the most preferred materials for designing enteric coating formulations in terms of performance and global acceptability (1). Aqueous enteric film coatings have been used widely in recent years. Many of these systems are pseudolatex dispersions of polymers such as CAP, latex dispersions of methacrylic acid copolymers and aqueous solutions of alkali salts (4).The advantages of an aqueous based coating system have been recognized. This is derived from the drawbacks of organic solvents including pollution, explosion hazards, and solvent toxicity. Especially there are risks for operators (5). Almost all nonsteroidal anti-inflammatory drugs irritate gastric mucosa and enhance ulceration by blocking protective action of the prostaglandins on gastric mucosa, causing ulcer formation not only in stomach but also in lower part of oesophagus and in duodenum too (6). The most important side effects of flurbiprofen include peptic ulceration, hemorrhage and perforation (7).The aim of current investigation was to develop an enteric coated flurbiprofen tablet formulation to minimize the gastric intolerance caused by flurbiprofen on long term use and to improve patient compliance by utilizing Acryl-Eze. Acryl-Eze is an optimized, one-step, pigmented, aqueous acrylic system for the application of an enteric film coating for oral solid dosage forms. Acryl-Eze combines the benefits and performance of a globally accepted enteric polymer (Eudragit® L100-55) with a fully formulated coating system, providing significant time savings in both development and production. Acryl-Eze has further been optimized for either tablet or multiparticulate applications (8). Eudragit® L100-55 is a copolymer of methacrylic acid and ethyl acrylate (1:1 ratio) which meets the USP definition for Methacrylic Acid Copolymer Type C. L100-55 is a re-dispersible powder produced by spray drying Eudragit® L30-D. Film coatings prepared from such dispersions are resistant to gastric juice but readily dissolve at a pH above 5.5 (9). EudragitL100-55 has been used as a coating polymer in several studies (10,11,12).

Cardiovascular Disease Risk Associated With the Long-term Use of Depot Medroxyprogesterone Acetate

Background: Depot medroxyprogesterone acetate (DMPA) contraception is widely used all over the world; however, it may lead to a decrease in high‐density lipoproteins and an increase in low‐density lipoproteins (LDL) and triglycerides. These changes in lipid profile have a direct effect on cardiovascular disease risk. This study has been conducted to investigate the relationship between DMPA use and lipid profile, and the effect of worsening of lipid profile on fasting blood glucose. The objective of the present study is to ascertain the effects of DMPA on lipid profiles and Castelli indices, and to estimate the risk of cardiovascular disease in the women using progesterone‐only methods for contraception. Methods: This was a multicenter case‐control study including females of reproductive age. A total of 893 women were selected according to inclusion and exclusion criteria described below with the age range of 19‐49 years. Among these, 477 were females who were beginning DMPA for contraception whereas 416 were the matched controls of same age and socioeconomic status. The lipid profiles, Castelli indices and fasting blood sugar were evaluated before initiation of DMPA and thereafter at 3, 6, 9 and 12 months. Controls were also analyzed for the same parameters in the same manner as that of treated group. The results were analyzed by repeated measure analysis of variance followed by Tukeys post hoc test for the multiple comparisons. Results: The results showed statistically significant differences in all parameters of lipid profile, namely cholesterol (180.7 ± 38.8 versus 133.03 ± 14.8 mg/dL, and P = 0.000), LDL (120.04 ± 36.2 versus 94.27 ± 19.6 mg/dL, and P = 0.000), very low‐density lipoprotein cholesterol (24.6 ± 10.0 versus 20.99 ± 8.66 mg/dL, and P = 0.000), high‐density lipoprotein (39.67 ± 3.6 versus 44.13 ± 4.22 mg/dL, and P = 0.000), total cholesterol (713.05 ± 110.2 versus 569.19 ± 80.4 mg/dL, and P = 0.000), triglycerides (126.33 ± 48.8 versus 99.03 ± 30.6 mg/dL, and P = 0.000), Castelli index I (4.61 ± 1.2 versus 3.02 ± 0.31, and P = 0.000) and Castelli index II (3.08 ± 1.07 versus 2.13 ± 0.41, and P = 0.000) between treated and control groups, respectively. Serum glucose levels were significantly higher (P ≤ 0.001) among the cases of DMPA (84.6394 ± 7.425 mg/dL) compared with that in the control (77.822 ± 7.733 mg/dL). Conclusions: This study clearly revealed that there is an increase in all deleterious lipid parameters and a decrease in favorable lipid measures. Hence, it can be concluded that continued use of DMPA may predispose females to the risk of cardiovascular disease in the long run.

Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f 2) results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.

Development of in vitro - in vivo correlations for newly optimized Nimesulide formulations

Use of the human volunteers in bioequivalence studies is being discouraged by the Food and drug administration after the introduction of biowaiver approaches. In-vitro in-vivo correlation (IVIVC) with the level A is accepted for the registration of new molecules. In the present study deconvolution technique with numeric approaches was applied after compressing and in vitro validating the 100mg Nimesulide immediate, intermediate and slow release tablets. Single centered, crossover, randomized study was conducted in four phases with a two-week washout period to obtain the plasma drug concentration data after administrating test and reference products in male healthy volunteers. KineticaTM 4.4.1 (Thermoelectron corp, USA) was used for the calculation of two ways ANOVA with 90% CI from both log transformed and non- transformed data and Phoenix WinNonlin 7 and its IVIVC toolkit version 7.0 was used for the application of numeric approaches of IVIVC. Results revealed that the individual internal percentage prediction error for AUCinf and Cmax were found to be < 15% while their average values were < 10% in all medium. Numeric values of % PE at pH 6.8 and pH 7.4 (50 rpm in USP II and 100 rpm in USP I and II apparatus) were found to be (2.5842, 2.9789 and, 7.1732; 7.0944, 2.4721 and 4.350) for AUCinf and (2.5842, 0.5736 and 4.6928; 5.6214, 3.0551 and -2.4711) values for Cmax respectively. The low values of prediction errors demonstrate that the correlation model is projecting the in vivo response of each formulation. Percentage External error (% PE) was not required because individual values of percentage internal error (%PE) of Cmax and AUClast were not >15. In order to predict point to point correlation between fraction drug dissolved and drug absorbed, their mean r2 value was found to be > 0.9112 which showed a linear correlation in slightly alkaline pH.

Design, Development, and Optimization of Dexibuprofen Microemulsion Based Transdermal Reservoir Patches for Controlled Drug Delivery

The aim of the study was to develop a reservoir-type transdermal patch for a controlled delivery of dexibuprofen and to evaluate its in vivo anti-inflammatory activity in Albino Wistar rats. In order to develop these patches, six formulations of dexibuprofen microemulsion comprising ethyl oleate, Tween 80: PG (2 : 1), and water were prepared by simplex lattice design and characterized. The reservoir compartment was filled with these microemulsions and in vitro release and skin permeation were assessed. The optimized patch was obtained on the basis of the responses: Q24 and flux. The impact of drug loading, surface area, membrane thickness, adhesive, and agitation speed on drug release and permeation was also studied. The skin sensitivity reaction and in vivo anti-inflammatory activity of optimized patch were evaluated. Stability study at three different temperatures for three months was carried out. The result suggests that a membrane based patch with zero-order release rate, Q24 of 79.13 ± 3.08%, and maximum flux of 331.17 µg/cm2h can be obtained exhibiting suitable anti-inflammatory activity with no visible skin sensitivity reaction. The outcomes of stability study recommend storage of patches at 4°C having shelf-life of 6.14 months. The study demonstrates that the reservoir-type transdermal patch of dexibuprofen microemulsion has a potential of delivering drug across skin in controlled manner with required anti-inflammatory activity.

A Stability-Indicating High Performance Liquid Chromatographic Assay for the Simultaneous Determination of Pyridoxine, Ethionamide, and Moxifloxacin in Fixed Dose Combination Tablets

Stability indicating reversed phase HPLC method was developed and validated for the simultaneous quantitation of antitubercular drugs, ethionamide (ETH), and moxifloxacin (MOX) with commonly coprescribed vitamin, pyridoxine (PYR) in tablet dosage form. The method was found rapid, precise and accurate. The separation was performed in Hibar 150-4.6, Purospher STAR, RP-18e (5 μm) column, using mobile phase A (0.03 M sodium citrate adjusted to pH 5 with glacial acetic acid) and mobile phase B (100% methanol), ran at variable proportions at flow rate of 1.0 mL/min. The detection was carried out at 320 nm. The method was observed linearly in the range of 2.5–17.5 μg/mL for PYR, 25–175 μg/mL for ETH, and 40–280 μg/mL for MOX with respective limits of detection/quantitation of 0.125 μg/mL/1.28 μg/mL, 0.25 μg/mL/2.56 μg/mL, and 0.35 μg/mL/3.65 μg/mL. The drugs were also subjected to oxidative, hydrolytic, photolytic, and thermal degradation; the degradation products showed interference with the detection of PYR, ETH, and MOX. The proposed method was observed to be effective to quantitate MOX (400 mg), ETH (250 mg), and PYR (25 mg) in fixed dose combination tablet formulation.