Open Access Original Research Article

Biochemical Changes Induced by the Toxicity of Variable Sizes of Silver Nanoparticles

Qais Jarrar, Abdelkader Battah, Fatima Obeidat, Khairat Battah

Journal of Pharmaceutical Research International, Page 2670-2678
DOI: 10.9734/BJPR/2014/14666

Background: Silver nanoparticles (SNPs) rapid involvement in industry and nanomedicine increased human exposure to variable forms of these particles, with possible potential risk on human health.
Aims: The aim of this study is to investigate the biochemical changes induced by variable sizes of SNPs toxicity.
Place and Duration of Study: Faculty of Medicine, The University of Jordan and the College of Applied Medical Sciences at Aljouf University, Saudi Arabia, between January 2013 and January 2014.
Study Design: Forty-two male mice were subjected to a daily single dose (1mg/kg body weight) of SNPs using five different sizes (10 nm, 20 nm, 40 nm, 60 nm and 100 nm) for 35 days.
Methodology: Biochemical changes of the following eleven biochemical tests were determined: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglycerides, total bilirubin, creatinine, total protein, albumin, urea, uric acid and total cholesterol.
Results: Silver nanoparticles significantly elevated aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglycerides, total bilirubin and creatinine, with no significant change in total protein level while albumin and total cholesterol levels were lowered.
Conclusion: The findings indicate that exposure to SNPs produced significant biochemical changes that might affect the functions of the vital organs. Moreover, these alterations were size-dependent with smaller particles (10 nm and 20 nm) induced more alterations than the larger ones.

Open Access Original Research Article

Preparation of Metformin Hydrochloride Extended Release Matrix Tablets by Direct Compression Method and Its In vitro Evaluation

Mohammad Raquibul Hasan, Md. Abul Hossen, Aumit Roy, Tufikul Islam, Md. Saiful Islam Pathan

Journal of Pharmaceutical Research International, Page 2679-2693
DOI: 10.9734/BJPR/2014/14013

Aims: Metformin Hydrochloride, a biguanide, is an orally active antihyperglycemic agent, used in the treatment of non-insulin dependent diabetes mellitus (NIDDM). It has relatively short plasma half life, low absolute bioavailability. Extended release formulation of Metformin Hydrochloride by direct compression method has significant challenges due to its poor inherent compressibility and high dose. The aim of this study was to develop extended release tablets of Metformin Hydrochloride by direct compression method and In vitro evaluation.
Study Design: Nine different formulations were made by varying drug-polymer ratio and were subjected to different physical property tests of the powder blend as well as prepared tablets, followed by dissolution test.
Place and Duration of Study: Department of Pharmacy, State University of Bangladesh, Dhaka, Bangladesh, between January 2013 and July 2013.
Methodology: Nine formulations of Metformin Hydrochloride matrix tablets - F-1, F-2, F-3, F-4, F-5, F-6, F-7, F-8 and F-9 - were prepared by direct compression method using release retarding materials, Methocel K100 MCR Premium (derivative of hydroxypropyl methylcellulose - HPMC) and Xanthan gum. The drug and polymer ratio were 1:0.41, 1:0.45, 1:0.49, 1:0.59, 1:0.63, 1:0.67, 1:0.77, 1:0.81 & 1:0.85 respectively. The micromeritic behavior of the powder blends were evaluated for bulk density, angle of repose, compressibility index along with post compressional attributes of the tablets such as thickness, hardness, friability, weight variation and content of Metformin Hydrochloride in the tablets. The in-vitro drug release study was carried out in 1000 mL phosphate buffer medium (pH 6.8) at 37±0.5°C at 100 rpm for 10 hours using USP Apparatus Type-II (paddle) method.
Results: FT-IR study showed drug-excipient compatibility and DSC analysis showed no solid state interaction between components. The physical properties of the powder blend and the tablets were within the acceptable limits. Maximum and minimum drug release were found in formulation F-1 and F-9 respectively which indicate that release rate is inversely proportional to the concentration of Methocel K100 MCR Premium and Xanthan gum in combination. Dissolution study also showed that, formulations F-7, F-8 & F-9 do not comply with drug release specification of USP and among the rest six formulations F-3, F-4 & F-5 comply better with drug release specification of USP. After fitting the data to Korsmeyer-Peppas equation we found that diffusion along with erosion could be the mechanism of drug release.Considering the micromeritic behaviour of the powder blend, physical attributes of the compressed tablets, and dissolution, formulation F-4 seemed most suitable.
Conclusion: Extended release Metformin Hydrochloride tablets can be produced to overcome frequent dosing related problems. However, Further study on formulation optimization and scale up, stability and bioequivalence is needed to confirm the appropriateness of these formulated extended release tablets.

Open Access Original Research Article

Anti-Diarrhoea Property of Crude Aqueous Leave Extract of Red Apple Psidium guajava in Castor Oil-Induced Diarrhoea in Rats

Okere O. Shekins, Iliemene Uju Dorathy

Journal of Pharmaceutical Research International, Page 2694-2701
DOI: 10.9734/BJPR/2014/13297

Objective: To investigate the anti-diarrhoea property of aqueous leaves extract of Psidium guajava (red apple guava leaves) in castor oil-induced diarrhoea in rats.
Methods: Five groups of five rats each orally received the following treatment; groups II, III & IV received 100, 200 & 400 mg/kg body weight of the extract respectively and group V received a standard drug for diarrhoea (Laperamide), while group 1 received 1ml of castor oil only without treatment. 1 ml of castor oil was given to rats in all groups, one hour after the treatment with extract and standard drug. The rats in each group were then placed singly in a cage with adsorbent paper on the floor of the cage. The diarrhoea episode was observed for 4 hours and the cumulative frequency of the wet and formed stools were noted at the end of the 4th hour. Percentage inhibition of diarrhoea was calculated using the mean stool frequency and the anti-diarrhoea activity determined in terms of percentage protection.
Results: The extract reduced stooling in castor oil induced diarrhoea in rats in group IV which shows no significant difference with the group V treated with standard drug. The rats in group I showed the highest stooling episode which is significantly higher than all other groups.
Conclusion: These findings suggest that an aqueous extract of guava leaves may be used as an effective treatment for non specific diarrhoea in medicine. The anti-diarrhoea action may be linked to direct inhibitory effect of the extract on the propulsive movement of the gastrointestinal tract smooth muscles. It equally shows that the treatment is dose dependent.

Open Access Original Research Article

Effect of Delphinium staphisagria in Murine Infection by Myocoptes musculinus

W. C. Eibel, F. Otomura, A. R. T. Pupulin

Journal of Pharmaceutical Research International, Page 2702-2710
DOI: 10.9734/BJPR/2014/14294

Biomedical investigations still rely on the use of laboratory animals, mice and rats are the most commonly used on experimentations. Past experimentations with these animals showed that they could be affected by environmental conditions and infections, causing interferences on researches. Colonies of mice and rats can be parasitized by ectoparasites. Ectoparasites may interfere with scientific researches, typically exacerbated when the animals are immunosuppressed, however, is not common to cause mortality on mice. The plant known as Delphinium staphisagria has been used for years on the treat of skin wounds caused by insects and other parasites such as scabies. The aim of this study is to evaluate the effectiveness of the plant Delphinium staphisagria on Myocoptes musculinus infections on mice (Mus muscullus), the experimental animal. The mice of the Parasitology Lab / DBS / UEM with four weeks of age, weighing approximately 28-30 g were evaluated for clinical diagnosis of infection Myocoptes musculinus. Once confirmed, the parasitic animals were divided into experimental groups consisting of 10 animals each as: (I) infected animals with Myocoptes musculinus untreated, (II) infected animals treated with Delphinium staphisagria, once daily added in drinking water, (III) animalsco-infected with strain of low lethality of Trypanosoma cruzi and treated with Delphinium staphisagria. (IV) animalsco-infected with low lethality strain of T. cruzi and untreated. The clinical and parasitological evaluation was conducted for 90 days. All animals treated with Delphinium staphisagria showed clinical and parasitological cure for the infection of Myocoptes musculinus.

Open Access Original Research Article

The Application of Factorial Experimental Design in Capsule Coating for Potential Colon Targeting of an Antiamebic Drug

N. C. Obitte, A. Chukwu

Journal of Pharmaceutical Research International, Page 2711-2728
DOI: 10.9734/BJPR/2014/7076

Aim: The application of factorial experimental design to evaluate the effect of particle size, capsule surface coating and binder concentration on the in vitro controlled release profile of metronidazole from encapsulated granules.
Methodology: Metronidazole granules were prepared by the wet granulation technique and encapsulated in hard gelatin capsule shells. Eudragit® L-100 and Landolphia owariensis latex served as primary and secondary coatings respectively on 50 or 75% of capsule surface. The three formulation factors (% capsule surface coating, matrix former concentration and particle size) were subjected to a 2x3x4 factorial design experiment using the software (JMP 4.0.4, SAS Inc. USA). Gradient drug release studies were conducted in three media; firstly in media of pH 1.2 for 2 h, pH 6.8 for 3 h and finally pH 7.4 until exhaustion of drug release. The drug release data were subjected to kinetic treatment to establish operational release kinetics such as zero order, first order, Higuchi, Hixon Crowell and Kitazawa, while the power law enabled the prediction of mechanism of drug release.
Results: Results showed that % capsule surface coated with Landolphia owariensis latex and particle size significantly (p<0.05) contributed to time of drug release (T7.4) at pH 7.4. In tandem with this, maximum amount of drug released (D7.4) at pH 7.4 was significantly (p<0.05) affected by particle size alone. A few batches were characterized by anomalous transport while over 80% were associated with super case 11 type of release.
Conclusion: We therefore conclude that, factorial experimental design identified Landolphia owariensis latex coating and particle size of granules as being chiefly responsible for drug release variations.