International Journal of Pharmaceutical Investigation : 2011 - 1(3)

Plagiarism: An editor's concern

Javed Ali — Wed,12 Oct 2011

Javed Ali

International Journal of Pharmaceutical Investigation 2011 1(3):129-130

Insulin chewing gum: Need of the day for diabetic patients

Uday Venkat Mateti — Wed,12 Oct 2011

Uday Venkat Mateti, Nagesh Adla, Thiyagu Rajakannan, Rajesh Valakkathala

International Journal of Pharmaceutical Investigation 2011 1(3):131-134

Chewing gum is an excellent drug delivery system for self medication as it is convenient, can be administered discreetly without water and offers the removal of 'needle fear' for the patients. As it releases insulin orally, it helps in tackling of the deprivation of insulin by digestive enzyme without adding digestive enzyme inhibitor. This can be done by binding of vitamin B12 and insulin. The vitamin B12 is protected with haptocorrin which is a salivary protein. Another chemical pathway takes over to help vitamin B12 pass into the bloodstream as haptocorrin reaches the intestines. The binding of vitamin B12 and insulin molecules makes the insulin to be protected on this supply chain. The insulin could ride all the way into the bloodstream, where it is released to do its work. By stimulating the brain, chewing gum also increases the releases of insulin. Finding simpler ways to deliver insulin into the blood stream is one important avenue for tackling the diabetes epidemic that is sweeping the developed world. The conditions in gastrointestinal tract may damage the body's protecting and absorbing mechanisms for the valuable molecules. Chewing gum would be a better delivery method in humans.

Solubility of aceclofenac in polyamidoamine dendrimer solutions

Jaydeep Patel — Wed,12 Oct 2011

Jaydeep Patel, Kevin Garala, Biswajit Basu, Mihir Raval, Abhay Dharamsi

International Journal of Pharmaceutical Investigation 2011 1(3):135-138

In the present study we investigated the effect of polyamidoamine (PAMAM) dendrimers on the aqueous solubility of aceclofenac. The aqueous solubility of aceclofenac was measured in the presence of dendrimers in distilled water. The effect of variables, such as pH condition, concentration, temperature and generation (molecule size) of dendrimer, has been investigated. Results showed that the solubility of aceclofenac in the dendrimer solutions was proportional to dendrimer concentration. The order in which the dendrimers increased the solubility at a constant pH condition was G3 > G0. The influence of dendrimer solution pH on the solubility enhancement of aceclofenac suggests that it involves an electrostatic interaction between the carboxyl group of the aceclofenac molecule and the amine groups of the dendrimer molecule. The solubility of aceclofenac was inversely proportional to the temperature of dendrimer solution.Different generation (G0 and G3) PAMAM dendrimers have the potential to significantly enhance the solubility of poor water-soluble drugs.

Nanocarrier-based hydrogel of betamethasone dipropionate and salicylic acid for treatment of psoriasis

Sanjula Baboota — Wed,12 Oct 2011

Sanjula Baboota, Md Sarfaraz Alam, Shrestha Sharma, Jasjeet K Sahni, Anil Kumar, Javed Ali

International Journal of Pharmaceutical Investigation 2011 1(3):139-147

Introduction: Betamethasone dipropionate (BD) has anti-inflammatory, immunomodulatory, and antiproliferative activity. The aim of the current work was to test the hypothesis that the addition of corticosteroid such as BD and a keratolytic agent such as salicylic acid in nanocarrier based microemulsions formulation would result in enhancement and sustaining of corticosteroid delivery rate leading to better anti-psoriatic activity. Clinical use of BD is restricted to some extent due to its poor permeability across the skin. So to increase its permeation across the skin, microemulsion-based gel formulations were prepared and characterised. Materials and Methods: Microemulsions were prepared by aqueous phase titration method, using oleic acid:sefsol (1.5:1), Tween 20, isopropyl alcohol, and distilled water as the oil phase, surfactant, cosurfactant and aqueous phase, respectively. Selected formulations were subjected to physical stability studies and consequently in vitro skin permeation studies. Surface studies of optimized formulation were done by transmission electron microscopy. In vivo anti-inflammatory activity was done by carageenan-induced raw paw edema method. Results: The droplet size of microemulsions ranged from 60 to 190 nm. The optimized formulation exhibited viscosity 28.55 ± 2.03 mP, refractive index 1.409, pH 6.4, and conductivity 10 -4 scm -1 . The optimized microemulsion was converted into hydrogel using carbopol 934, and salicylic acid was incorporated into it. Drug deposition in skin was found to be 29.73 μg/mg. Assessment of skin permeation was done by histopathology studies which indicated changes in the structure of epidermal membrane of skin. In vivo anti-inflammatory activity indicated 72.11% and 43.96% inhibition of inflammation in case of developed microemulsion gel and marketed gel, respectively. Conclusions: The developed microemulsion gel containing BD and salicylic acid provided sustained and good anti-inflammatory activity for the treatment of psoriasis.

Formulation and evaluation of sustained release bioadhesive tablets of ofloxacin using 3 2 factorial design

Hemant H Gangurde — Wed,12 Oct 2011

Hemant H Gangurde, Mayur A Chordiya, S Tamizharasi, K Senthilkumaran, T Sivakumar

International Journal of Pharmaceutical Investigation 2011 1(3):148-156

Background: Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from upper gastrointestinal tract and improve the bioavailability of medications that are characterized by narrow absorption window. The aim of current study was to design sustained release bioadhesive gastroretentive dosage form of ofloxacin. Materials and Methods: A 3 2 full factorial design was employed to systematically study the drug release profile and bioadhesive strength. Carbopol 934P and HPMC K100M were selected as the independent variables. Compatibility between drug and polymer was tested by fourier transform infrared (FTIR) and X-ray diffraction (XRD) techniques. Tablets were prepared by direct compression and were evaluated for tablet characteristics, swelling study, adhesion strength, percent drug released, radiographic imaging study and stability study. The optimized formulation was then compared with marketed formulation (Oflin OD®). Results: Tablets prepared showed good tablet characteristics, optimum swelling property, and good adhesion strength with high detachment force. Most of the formulations including the optimized formulation followed Higuchi kinetics and the drug release mechanism was found to be anomalous. Radiographic image proved that tablet remains intact in its structural integrity and shape in stomach up to 24 h. The short-term accelerated stability testing was carried out for the optimized formulation, and results revealed that drug content, in-vitro dissolution and all other parameters were within acceptable limits. Conclusion: Thus, the prepared bioadhesive gastroretentive ofloxacin tablet may prove to be a potential candidate which increases the bioavailability of ofloxacin for any intragastric condition.

Study on sustained-release metformin hydrochloride from matrix tablet: Influence of hydrophilic polymers and in vitro evaluation

Kamlesh J Wadher — Wed,12 Oct 2011

Kamlesh J Wadher, Rajendra B Kakde, Milind J Umekar

International Journal of Pharmaceutical Investigation 2011 1(3):157-163

The overall objective of the present work was to develop an oral sustained-release (SR) metformin tablet prepared by the direct compression method, using hydrophilic hydroxylpropylmethylcellulose (HPMC) and Guar gum polymer alone and in combination at different concentrations. Metformin hydrochloride (HCl), a biguanide, has a relatively short plasma half-life and low absolute bioavailability. All the batches were evaluated for thickness, weight variation, hardness and drug content uniformity and in vitro drug release. Mean dissolution time is used to characterize the drug release rate from a dosage form, and indicates the drug release-retarding efficiency of the polymer. The hydrophilic matrix of HPMC alone could not control the Metformin release effectively for 12 h whereas when combined with Guar gum, it could slow down the release of drug and, thus, can be successfully employed for formulating SR matrix tablets. Fitting the data to the Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release. Similarity factor ƒ2 values suggest that the test and reference profiles are identical.

In vitro and in vivo evaluation of chitosan buccal films of ondansetron hydrochloride

Marina Koland — Wed,12 Oct 2011

Marina Koland, R Narayana Charyulu, K Vijayanarayana, Prabhakara Prabhu

International Journal of Pharmaceutical Investigation 2011 1(3):164-171

Buccal films of ondanstron hydrochloride were fabricated from mucoadhesive polymer, chitosan, and polyvinyl pyrrolidone (PVP K30) for the purpose of prolonging drug release and improving its bioavailability. All fabricated film formulations prepared were smooth and translucent, with good flexibility. The weight and thickness of all the formulations were found to be uniform. Drug content in the films ranged from 98 - 99%, indicating favorable drug loading and uniformity. The inclusion of PVP K30, a hydrophilic polymer, significantly reduced the bioadhesive strength and in vitro mucoadhesion time of the films, although the degree of swelling increased. In vitro drug release studies in simulated saliva showed a prolonged release of over five to six hours for all formulations, except C4, with 99.98% release in 1.5 hours. Kinetic analysis of the release data indicated that the best fit model with the highest correlation coefficient for all formulations was the Peppas model. In vivo studies, on selected films in rabbits, were conducted, to determine the pharmacokinetic parameters such as C max , T max , and AUC 0-∞ , using model-independent methods with nonlinear least-squares regression analysis. The AUC and values of C max of ondansetron hydrochloride were found to be significantly greater (P < 0.005) than the selected films C2 and C3, as compared to those from the oral solution, thereby confirming improved bioavailability via the buccal route. The T max values were also significantly greater (P < 0.005), indicating the slower release of the drug from buccal films, thereby, providing prolonged effects. Good in vitro-in vivo correlation was observed with R 2 values exceeding 0.98, when the percentage of drug released was correlated with the percentage of drug absorbed.

Design and evaluation of colon targeted modified pulsincap delivery of 5-fluorouracil according to circadian rhythm

Dasharath M Patel — Wed,12 Oct 2011

Dasharath M Patel, Rushiraj H Jani, Chhagan N Patel

International Journal of Pharmaceutical Investigation 2011 1(3):172-181

Introduction: A modified pulsincap dosage form of 5-fluorouracil was developed to target drug to colorectal carcinoma according to daily oscillations of rate-limiting metabolizing enzyme dihydropyrimidine dehydrogenase. Materials and Methods: The capsule body was made water insoluble by exposing the body to formaldehyde vapor. A mixture of granules containing drug, superdisintegrant, and osmogen was filled in the capsule body. A hydrogel plug was fitted to the mouth of the treated body, and the untreated cap was fitted to the body which was coated with Eudragit S100. Developed formulations were evaluated for in vitro drug release in 1.2 pH (2 h), 6.8 pH (3 h), and 7.4 pH (up to 12 h) buffer solutions. A 2 3 full factorial design was used for optimization in which the type of hydrogel plug (X1), the type of osmogen (X 2 ), and the type of superdisintegrant (X 3 ) were selected as independent variables while, cap opening time, percentage drug released in 5(Q 5 ), 6(Q 6 ), and 12(Q 12) h were taken as dependent variables. Results: Dissolution data were fitted to various models to ascertain the kinetic of drug release. Regression analysis and analysis of variance were performed for dependent variables. The results of the F-statistics were used to select the most appropriate model. Conclusion: Formulation F 1 containing sodium starch glycolate, potassium chloride, and hydroxypropyl methylcellulose K4M plug was considered optimum since it showed more similarity to the theoretical predicted dissolution profile (f 2 = 77.33). The studies indicate that the formulation was effective in providing in vitro colon targeted release and controlled release after predetermined lag time.

Formulation and evaluation of bucco-adhesive tablets of sumatriptan succinate

R Indira Prasanna — Wed,12 Oct 2011

R Indira Prasanna, P Anitha, C Madhusudhana Chetty

International Journal of Pharmaceutical Investigation 2011 1(3):182-191

Background: A novel aspiration in treatment of migraine, to provide greater therapeutic effect, overcome the side effects by complex therapeutic regimen and to improve patient compliance upon administering bucco-adhesive tablet formulations of sumatriptan succinate which have not been tested literally. Materials and Methods: This study was designed to develop a bucco-adhesive tablet containing sumatriptan succinate using blends of different bio-adhesive polymeric combinations such as hydroxy propyl methyl cellulose K4M, sodium carboxy methyl cellulose, and Carbopol 934P with a backing layer of ethyl cellulose by a direct compression technique. Tablets were subjected to physico-chemical parameters, swelling index, surface pH, ex vivo bioadhesive force, in vitro drug release, ex vivo drug permeation, and stability in saliva. Results: Good results were obtained in all the evaluated parameters. The drug release of all formulation follows zero-order kinetics by a diffusion mechanism type. Stability studies in human saliva, ex vivo buccal permeation studies by using sheep and porcine buccal mucosa were carried out for the optimized formulation (S4 CP:HPMC 3:1). Conclusion: The developed buccal drug delivery system containing sumatriptan succinate might be the alternative routes available to bypass the first pass metabolism and might be a milestone in the therapy of migraine and among all formulations S4 shows good controlled release results correlated with ex vivo permeation studies.

Lallemantia reylenne seeds as superdisintegrant: Formulation and evaluation of nimesulide orodispersible tablets

Karan Malik — Wed,12 Oct 2011

Karan Malik, Gurpreet Arora, Inderbir Singh, Sandeep Arora

International Journal of Pharmaceutical Investigation 2011 1(3):192-198

Aim : Orodispersible tablets also known as fast dissolving tablets disintegrate instantaneously within the mouth and thus can be consumed without water. The present study was aimed to formulate orodispersible tablets of nimesulide by using Lallemantia reylenne seeds as natural superdisintegrant. Materials and Methods: Powdered lallemantia seeds were characterized for powder flow properties (bulk density, tapped density, carr's consolidation index, hausner ratio, angle of repose), swelling index, viscosity, pH, and loss on drying. The prepared tablets were evaluated for different tablet parametric tests, wetting time, water absorption ratio, effective pore radius, porosity, packing fraction, in vitro and in vivo disintegration time, in vitro dissolution and stability studies. Results and Discussion: Increase in Lallementia reylenne concentration had an appreciable effect on tablet hardness and friability which clearly indicated binding potential of the seeds. Water absorption ratio increased with increase in Lallemantia reylenne concentration from batch A1 to A4. Water uptake coupled natural polymer swelling could be the most probable mechanism for concentration dependent reduction in disintegration time by the Lallemantia reylenne seeds. Porosity of the formulated tablets was found to increase from batch A1-A4. The in vitro disintegration results were in line with in vivo disintegration results. Conclusion: It could be concluded that Lallemantia reylenne seeds could be used as natural superdisintegrant in the formulation of orodispersible tablets.