Open Access Original Research Article

Formulation and Evaluation of Metoprolol Tartrate Loaded Niosomes Using 23 Factorial Design

Sharmin Nahar, S. M. Ashraful Islam, Swarnali Islam Khandaker, Waheeda Nasreen, Ohinul Hoque, Irin Dewan

Journal of Pharmaceutical Research International, Page 1-17
DOI: 10.9734/JPRI/2018/42068

The purpose of this study was to formulate and evaluate metoprolol tartrate (MT) loaded liposomes using factorial design. Preparation of niosomal drug delivery of MT increased its bioavailability which led to being better therapeutic effects, reduced the frequency of dosing and decreased side effects of hypertensive patients. Ether injection method (EIM) and thin film hydration method (TFHM) were used for the preparation of all formulations as per full factorial design to study the effect of two independent variables X1 (amount of span-60), and X2 (amount of cholesterol) on three dependent variable Y1 (percent drug entrapment efficiency), Y2 (percent drug content) and Y3 (percent cumulative drug release) respectively. The relation between the dependent and independent variables was drawn out from the mathematical equation and response surface methodology (RSM). Statistical analysis was performed using ANOVA. Microscopic observation confirmed that all particles were uniform in size and shape. The particle size of niosomes measured by SEM was between 3 μm to 4.5 μm that given the evidence of large uni-lamellar vesicles formed by EIM and TFHM.The percent drug entrapment efficiency was found to be highest for formulations MTEIM-8 and MTTFHM-8 with values 97.11% and 95.56% respectively. In vitro dissolution studies were carried out in phosphate buffer (pH 6.8) for 8 hours at 100 rpm and maintained at 37 ± 0.50C according to USP-II paddle method and absorbance was taken at 226 nm.The probable drug release mechanism may be fickian (class I) diffusion as the correlation coefficient (R2) best fitted with zero order and release exponent (n) was less than 0.43.  The FTIR studies have been done to confirm no interaction along with drug and polymer. In vitro and ex vivo comparative studies showed that niosomes had controlled the release of drug for a longer period. Finally, it can be concluded that niosomes could be an effective vesicle for delivery of MT with increased bioavailability.

Open Access Original Research Article

Exploring the Effect of Caffeine on Decelerating the Lethargic Action of Diclofenac in the Treatment of Pain

Mst. Marium Begum, Rubel Hossain, Md. Sahab Uddin, Md. Sohanur Rahman, Md. Motiar Rahman, Rita Saha, Asma Tabassum, Rubaba Karim

Journal of Pharmaceutical Research International, Page 1-13
DOI: 10.9734/JPRI/2018/40988

Background: Diclofenac is used as a potential analgesic for mild to moderately severe pain including migraine pain. However, the common side effect of this drug (drowsiness) becomes bothersome for patients taking diclofenac on regular basis in order to get rid of migraine pain. This hinders a person’s daily routine and eventually causes loss of motivation for work. The central nervous system (CNS) stimulant activity of caffeine is thought to decelerate the undesirable effect of diclofenac.

Objectives: The main aim was to investigate the efficiency of caffeine in decelerating the lethargic action of diclofenac at different dose regimen in pain induced Swiss Albino mice model.

Method: Different doses of caffeine (5 mg, 25 mg and 50 mg/kg body weight) were administered with diclofenac potassium tablet (50 mg/kg body weight) orally in acetic acid-induced pain in Swiss Albino male mice. The efficacy of caffeine (with and without diclofenac potassium 50 mg) in reducing pain was evaluated by writhing test. The CNS stimulating activity of caffeine to minimize lethargic properties of diclofenac was determined by measuring reflex action and locomotion of mice via conducting righting reflex test and open field test. Mean of the total duration of various locomotor activities of mice of different test groups was compared with normal and control groups by using ANOVA and Dunnet's test.

Results: The results of all tests demonstrated the reduced lethargic behaviours in mice with the maximum dose of caffeine (50 mg) in combination with diclofenac potassium (50 mg) at the same time the study revealed the overall effect of caffeine in enhancing total locomotion of mice. The statistical data of test results showed that higher dose of caffeine (50 mg) in combination with diclofenac potassium (50 mg) significantly increased (P<0.01) locomotor activities of mice as compared to the normal group. Moreover, for writhing counts significant result (P<0.01) was found in the combination of caffeine 50 mg with diclofenac potassium 50 mg when compared to the control group.

Conclusion: The present investigation suggests that the combination of diclofenac potassium (50 mg) with caffeine (50 mg) possess potent analgesic activity and successfully minimize the side effects (drowsiness and dizziness) of diclofenac.

Open Access Original Research Article

An In-vitro Antioxidant and Antidiabetic Evaluation of Traditional Medicinal Plants of Botswana

Mmopi N. Keneilwe, George Saramma, Chabaesele Kelvin

Journal of Pharmaceutical Research International, Page 1-12
DOI: 10.9734/JPRI/2018/42218

The present study was aimed at the in-vitro analysis of the antioxidant and antidiabetic potential of the methanol extracts of four perennial plants which are indigenous to Botswana and further to investigate whether their antihyperglycemic effects are working through the antioxidant system. The plants used in this study were the aerial parts of Ocimum gratissimum, corms of Hypoxis hemerocallidea, aerial parts of Momordica balsamina and the leaves and stems of Lippiascaberrima. The extracts were prepared in 70% methanol and they were labeled as MEOG, MEHHC, and MEMB, MELS (l) and MELS (s) respectively. All the four plant extracts showed a notable antioxidant and antidiabetic activity, the most potent one being H. hemerocallidea and the least potent being L. scaberrima stems. The total antioxidant status was evaluated by DPPH, ABTS and TBA assays. Total phenolic content was determined for each extract and converted to mg of gallic acid equivalents/g of dry extract (mg GAE/g).The crude methanol extracts showed many components with high radical scavenging activity in the TLC-DPPH bioautogram. The antidiabetic potential was determined by evaluating the inhibition of the extracts on α-amylase activity, and the results indicated that MEHHC showed the highest effect followed by MEMB, MEOG MELS (l) and MELS(s). The results obtained in the present investigations indicated that the extracts used in this study have bioactive compounds with antioxidant and antidiabetic properties.

Open Access Original Research Article

Antipsychotic Effects of Ethanol Leaf Extract and Fractions of Milicia excelsa (Moraceae) in Mice

Lateef Abiola Akinpelu, Moses Atanda Akanmu, Efere Martins Obuotor

Journal of Pharmaceutical Research International, Page 1-10
DOI: 10.9734/JPRI/2018/42383

Aim: This study investigated the acute toxicity (LD50) and antipsychotic potentials of ethanol leaf extract of Milicia excelsa (EME), hexane (HF), ethyl acetate (EAF), butanol (BF) and aqueous (AF) fractions in mice.

Study Design: This study used experimental mice models predictive of human psychosis.

Place and Duration of Study: Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria, between January 2014 to February 2015.

Methodology: The antipsychotic effect was assessed using swim-induced grooming; apomorphine-induced climbing and ketamine-induced hyperlocomotion behaviours in mice.

Results: The results showed that the LD50 of the ethanol extract and its various fractions were greater than 5000 mg/kg. EME and all its fractions significantly (P < 0.05) decreased the number of grooming while the duration of grooming was significantly (P < 0.05) reduced by EME, EAF and AF in swim-induced grooming. EME and EAF significantly (P < 0.05) inhibited climbing behaviour in apomorphine-induced climbing. EME and all the fractions significantly (P < 0.05) inhibited the hypermotility induced by ketamine while the number of ataxia was significantly (P < 0.05) reduced by EME, EAF and AF in ketamine-induced hyperlocomotion, with AF producing a stronger ataxia reducing effect compared to haloperidol, a reference antipsychotic drug. EME and EAF showed consistent antipsychotic activities in all the models used.

Conclusion: This study concludes that EME and all its fractions may be safe and contain antipsychotic principles, thus, providing scientific evidence for the suggested ethnomedicinal use of the leaf in treating insanity in traditional medicine.

Open Access Original Research Article

A Novel HPLC Method for Determination of Phenytoin in Human Plasma

Jesse Flores, Sheril Alexander, Mariana Babayeva

Journal of Pharmaceutical Research International, Page 1-7
DOI: 10.9734/JPRI/2018/41885

Aim: Aim of this research was to develop and validate a simple, efficient and reproducible high-performance liquid chromatography method to measure phenytoin concentrations in human plasma

Study Design: Linearity, selectivity, sensitivity, accuracy and precision of the analytical methods were validated according to ICH guidelines.

Methodology: The method employed a Phenomenex C18 column kept at 25ºC. The mobile phase consisted of a 0.05 M potassium dihydrogen phosphate buffer solution (pH 2.8) and methanol in a ratio of 60:40, respectively. The flow rate of the mobile phase was 0.7 mL/min. Phenytoin was detected at a wavelength of 250 nm.

Results: Phenytoin was eluted at 7.4 minutes with no interference with the other components of the human plasma. The method was linear in the range of 1-25 μg/mL (R2 = 0.9998). The LOD and LOQ were calculated as 0.07 μg/mL and 0.20μg/mL, respectively. Recovery, tested in the range of 5-20 μg/mL, was found to be 99.21 - 102.09%. Intraday and interday precision RSDs were 0.65 and 0.29%, respectively.

Conclusion: The proposed method is fast, reliable and reproducible, and can be recommended to measure free phenytoin levels in the blood.