Open Access Short Research Article

Spectrophotometric Estimation of Cilnidipine in Tablets

Mohammed M. Safhi

Journal of Pharmaceutical Research International, Page 451-456
DOI: 10.9734/BJPR/2015/19275

Aim: The paper discusses the Spectrophotometric method developed to determine Cilnidipine in pharmaceutical formulation.

Methodology: The method depends on the reaction of the nitro group of the drug with Potassium Hydroxide in Dimethyl Sulphoxide (DMSO) medium to form a coloured product, which shows maximum absorbance at 425 nm. It also Common excipents used in the formulation bear no effect on the proposed method. The authenticity and performance of the proposed method is approved by point and interval hypothesis tests and through recovery studies.

Results: The linear regression equations obtained by applying least square regression analysis for Cilnidipine were r2= 0.9997 and adheres Beer’s Law in the concentration range of 1– 9 μg/ml.

Conclusion: The method was validated for specificity, linearity, accuracy, precision, Limit of detection and limit of quantification are found to be suitable to be employed in Quality Control as per the International Conference on Harmonization guidelines.

Open Access Original Research Article

Synthesis and Evaluation of the Schistosomicidal and Trypanocidal Properties of Thioxo-Imidazolidines and Thiazolidin-2, 4-Diones

Jamerson Ferreira de Oliveira, Anekécia Lauro da Silva, Antônio Sérgio Alves de Almeida Junior, Edna de Farias Santiago, Sheilla Andrade de Oliveira, Vinícius Barros Ribeiro da Silva, Aline Caroline da Silva, Andrea Ferreira de Barros, Valéria Rêgo Alves Pereira, Ivan da Rocha Pitta, Maria do Carmo Alves de Lima

Journal of Pharmaceutical Research International, Page 386-400
DOI: 10.9734/BJPR/2015/18983

Aims: Synthesis and evaluation of the schistosomicidal and trypanocidal properties of thioxo-imidazolidines and thiazolidin-2,4-diones.

Study Design: We tested this compounds by way of in vitro evaluation against the adult worms of Schistosoma mansoni and forms of Trypanosoma cruzi.

Place and Duration of Study: Departamento de Antibióticos, Universidade Federal de Pernambuco and Fundação Oswaldo Cruz/PE between January 2013 and March 2014.

Methodology: This study was approved by the Ethics Committee on Animal Use Research authorized by the license number. 38/2012. The thiazolidine (5a-h) and imidazolidine (7a-d) compounds tested for its cytotoxicity to mouse splenocytes. Then the compounds were evaluated against adult worms of S. mansoni by performing the activity in vitro at doses 5-100 µg/mL. In addition, the derivatives were evaluated against epimastigote and trypomastigote forms of Trypanosoma cruzi (1.23-100 µg/mL).

Results: It was found that 7a derivate imidazolidine and 5f thiazolidine caused a high efficiency in terms of the mortality of S. mansoni (100%) in the first 24 hours of the experiment. In the trypanocidal activity, the thiazolidine compounds 5f and 5h exhibited satisfactory activity through their high effectiveness against the epimastigote (0.98 and 1.36 μg/mL) and trypomastigote (0.43 and 1.58 μg/mL) forms. Of the imidazolidine compound tested, derivative 7d stood out from the others in terms of its activity against the trypomastigote form, with IC50 of 1.26 μg/mL.

Conclusion: The imidazolidine and thiazolidine derivatives tested are potential schistosomicidal and trypanocidal drugs, although more advanced experiments involving in vivo assays are still required.

Open Access Original Research Article

mAb Higher Order Structure Analysis with Protein Conformational Array ELISA

Michael Davies, Gan Wang, Guofeng Fu, Xing Wang

Journal of Pharmaceutical Research International, Page 401-412
DOI: 10.9734/BJPR/2015/18952

The clinical and biological properties of protein-based therapeutics, or biologics, are closely related to their Higher Order Structures (HOS) which in turn can be altered by many physical and chemical conditions. A novel technology to monitor changes in monoclonal antibody (mAb) HOS is the Protein Conformational Array (PCA) ELISA which uses a bank of more than 30 antibodies to measure protein epitope change on the surface of the mAb. Using this technology, this report provided interesting findings for the first time on the HOS changes in response to the various conditions often encountered during mAb formulation development. Specifically, one IgG1 and four IgG2 native molecules in formulation buffer were compared with the same IgG which had undergone exposure to increased temperature, pH extremes and light exposure. In addition, we also examined the impact of glycation and de-glycosylation on the mAb HOS. This study demonstrated that the PCA ELISA is stability-indicating and can provide detailed HOS information that could be important for the successful development of monoclonal antibodies.

Open Access Original Research Article

Mucoadhesive Potentials of a Natural Polymer Obtained from the Seeds of Dioclea reflexa in Aminophylline Tablet Formulations

C. C. Mbah, C. Udekwe, P. F. Builders, M. A. Momoh, O. O. Kunle

Journal of Pharmaceutical Research International, Page 413-427
DOI: 10.9734/BJPR/2015/15661

Aim: The mucoadhesive potentials of a natural gummy polysaccharide obtained from the seeds of Dioclea reflexa Hook F., (Fam.: Papilionaceae) (DR) was evaluated under varying pH conditions using aminophylline tablet formulations.

Study Design: The work was designed to experimentally evaluate the mucoadhesive effects of DR in comparison with that of a synthetic polymer, hydroxypropyl methylcellulose (HPMC).

Place and Duration of Study: The study was carried out in the Department of PT & RMD of NIPRD, Idu, Abuja, Nigeria between May 2011 and June 2012.

Methodology: The tablets were prepared by the wet granulation method using 1% w/w of the polymers as binders and 2.5% w/w as coating solutions, respectively. Some basic tablet characteristics were evaluated following standard procedures. In vitro drug release was also assessed after tablet coating. The mucoadhesive potentials at various pH levels: 1.2, 4.0, 6.5, 7.4 and 9.2, corresponding to those of the different gastrointestinal tract compartments, were evaluated by the wash-off method. The results were analyzed by analysis of variance (ANOVA) and t-test at P = .05.

Results: The release profiles showed that coating caused prolongation up to 8 h for both DR- and HPMC-coated tablets with the latter having significantly (P < .05) higher rates from 0.25 to 6 h (86.23±0.50: 44.10±0.31% and 101.71±0.20: 94.15±0.33% in 1 and 6 h for HPMC and DR tablets, respectively). The mucoadhesive potentials of DR were generally less than that of HPMC over the range of pH tested, except at 6.5 where it performed significantly (P < .05) better.

Conclusion: DR is useful as a mucoadhesive pharmaceutical excipient in aminophylline tablet formulations. It had optimum and better mucoadhesive strength than HPMC at the pH of 6.5 but less at 1.2, 4.0, 7.4 and 9.2.

Open Access Original Research Article

Formulation and Evaluation of Sustained Release Gastro-retentive Drug Delivery System of Acyclovir Leading to Enhanced Bioavailability

Sunil Kumar Mishra, Smriti Khatri

Journal of Pharmaceutical Research International, Page 428-439
DOI: 10.9734/BJPR/2015/19116

Objective: The objective was formulation and characterization of low-density gastro-retentive microspheres of Acyclovir (ACV) using hydroxyl propyl methyl cellulose to enhanced retention time and bioavailability.

Materials and Methods: HPMCK4M was used as polymer for forming microspheres and Poly Vinyl Alcohol as stabilizing agent. The microspheres were characterized with respect to their morphology, particle size, encapsulation efficiency, production yield, in-vitro release and pharmacokinetic study in rats. The mean particle size was within range and showed spherical shape.

Results and Discussion: Microspheres were having sufficient entrapment efficiency and floating ability and were directly proportional to the polymer concentration. In-vitro and pharmacokinetic study in rats proved the efficiency of microspheres in sustaining the drug release for 12 hrs as compared to oral suspension of ACV.

Conclusion: The floating microspheres of ACV are potential drug delivery system for the enhancement of oral bioavailability of ACV.

Open Access Original Research Article

Formulation and Evaluation of Ezetimibe Liquisolid Tablets: An Approach to Enhance the Dissolution Rate

Sateesh Kumar Vemula, Saritha Aila, Vijaya Kumar Bontha

Journal of Pharmaceutical Research International, Page 440-450
DOI: 10.9734/BJPR/2015/19125

Background and the Purpose of the Study: Liquisolid compacts’ using poorly water soluble drugs is considering as one of the novel pharmaceutical formulation technologies to improve the dissolution rate. This study was intended to improve the dissolution rate of ezetimibe by preparing liquisolid tablets.

Methods: In the preparation of liquisolid tablets, the following materials are used as carrier powder; polyethylene glycol (PEG) 400, tween 80 and propylene glycol as solvent, Avicel PH102 or starch or HPMC or PEG 4000 or PEG 6000 and Aerosil 200 are used as coating material. The interaction between drug and excipients was examined by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). In vitro drug release studies of liquisolid and conventional tablets (control) were conducted and compared the both to study the improvement in dissolution rate. Then the best formulation was subjected to stability studies.

Results and Discussion: The results of DSC and FTIR studies revealed that there are no possible drug-excipient interactions. The percentage drug release of ezetimibe at 10 min (Q10) and dissolution efficiency were increased from 23.86±1.08% and 11.61 for conventional tablet to 92.57±1.12% and 60.30 for the liquisolid formulation. From the stability studies, the similarity factor was found as above 50 that revealed the stability of the formulation.

Conclusion: In conclusion, the liquisolid technique was believed as a capable approach to enhance the ezetimibe dissolution rate.

Open Access Original Research Article

Diverse Data Sets Can Yield Reliable Information through Mechanistic Modeling: Salicylic Acid Clearance

G. M. Raymond, J. B. Bassingthwaighte

Journal of Pharmaceutical Research International, Page 457-473
DOI: 10.9734/BJPR/2015/19156

This is a practical example of a powerful research strategy: putting together data from studies covering a diversity of conditions can yield a scientifically sound grasp of the phenomenon when the individual observations failed to provide definitive understanding. The rationale is that defining a realistic, quantitative, explanatory hypothesis for the whole set of studies, brings about a “consilience” of the often competing hypotheses considered for individual data sets. An internally consistent conjecture linking multiple data sets simultaneously provides stronger evidence on the characteristics of a system than does analysis of individual data sets limited to narrow ranges of conditions. Our example examines three very different data sets on the clearance of salicylic acid from humans:  a high concentration set from aspirin overdoses; a set with medium concentrations from a research study on the influences of the route of administration and of sex on the clearance kinetics, and a set on low dose aspirin for cardiovascular health. Three models were tested: (1) a first order reaction, (2) a Michaelis-Menten (M-M) approach, and (3) an enzyme kinetic model with forward and backward reactions. The reaction rates found from model 1 were distinctly different for the three data sets, having no commonality. The M-M model 2 fitted each of the three data sets but gave a reliable estimates of the Michaelis constant only for the medium level data (Km = 24±5.4 mg/L); analyzing the three data sets together with model 2 gave Km = 18±2.6 mg/L. (Estimating parameters using larger numbers of data points in an optimization increases the degrees of freedom, constraining the range of the estimates). Using the enzyme kinetic model (3) increased the number of free parameters but nevertheless improved the goodness of fit to the combined data sets, giving tighter constraints, and a lower estimated Km = 14.6±2.9 mg/L, demonstrating that fitting diverse data sets with a single model improves confidence in the results. This modeling effort is also an example of reproducible science available at html:// webmodel/NSR/SalicylicAcidClearance