PHYSICO-MECHANICAL AND RELEASE PROPERTIES OF SUSTAINED RELEASE ARTESUNATE TABLETS IN HYDROXYPROPYL METHYLCELLULOSE MATRIX

Objective: This work was aimed at formulating artesunate tablets with hydroxypropyl methylcellulose (HPMC)-a hydrophilic polymer for the purpose of achieving a sustained release profile of the drug and evaluating their properties. Methods: The solubility profile of artesunate was determined in water, methanol, ethanol, ethanol/water mixtures (50/50, 40/60 v/v), simulated intestinal fluid (SIF) without enzymes (pH 7, 7.2 and 8), simulated gastric fluid (SGF) without enzymes (pH 1.2), 0.1N hydrochloric acid (HCI), 0.1N sodium hydroxide (NaOH), 0.1N acetic acid and phosphate buffer solution, PBS (pH 7, 7.2 and 8). Four batches of oral sustained release artesunate tablets intended for once-daily dosing were formulated with 10%, 20%, 25% and 30% w/w concentrations of HPMC using wet granulation method. Evaluation of granule properties was done by determining the angle of repose, flow rate, bulk density, tapped density, Carr's index and Hausner's quotient. The compressed tablets were also evaluated using official and non-official parameters. Absolute drug contents were determined in 0.1N NaOH, ethanol and methanol. In vitro release was studied in different media and release kinetics mechanism elucidated. In vivo studies were carried out using healthy Wistar rats. Results: Artesunate was observed to exhibit solubility at varying degrees depending on solvents or media employed as well as the pH of the media. All the granule batches have Hausner's quotient value of approximately 1.2. The values for Carr's index for all the batches ranged between 30 and 40. The angle of repose, Carr's index and Hausner's quotient values indicate good flow properties of the granules for all the batches. All the tablet batches conformed to official standard in terms of weight uniformity as no single tablet deviated beyond 5% from the average weight in each batch with no significant difference in the values (p>0.05). Values of hardness increased insignificantly from batches A to D (p>0.05). Friability values were very low and follows no specific pattern among the batches but the difference in the values was significant (p<0.05). Absolute drug content reduced while in vitro release times increased as hardness increased, indicating the probable progressive reduction in the tendency of the matrix to release the drug as the concentration of HPMC increased from batches A to D. n values obtained from analysis of release mechanism were above 0.89 for each batch. Conclusion: The release mechanism was shown to be complex and the release involved zero order, first order, and Higuchi model kinetics. The biological half-life of artesunate was shown to be 1.05 hr, and metabolites which bear resemblance to artesunate in absorbance seem to be encountered. In this work, HPMC matrix yielded high-quality tablets indicating its usefulness in sustained released product development

Evaluation of Physico-Mechanical and Mucoadhesive Properties of Biopolymer Films From Cola Acuminata Gum

Background: Applications of film-forming materials in coating technology and drug delivery systems has led to several investigations into the film-forming potential of different polymers. A good film-forming material must possess good mechanical strength, wetting and adhesive propertiesObjective: This study investigated the physico-mechanical and bioadhesive properties of biopolymer films from Cola accuminata pods, obi (Yoruba), oji (Ibo) and gworo (Hausa).Methodology: The Cola acuminata gum (CAG) was extracted by soaking the sliced pods in distilled water and precipitating with acetone. Plasticizer-free CAG mucilage (10% w/v) was prepared using aqueous dispersion method. Similar batches of CAG mucilage containing plasticizers - propylene glycol (PPG) or glycerin (G) at concentrations of 1 - 3% v/v of the mucilage were also prepared using the same method. The mucilage samples were cast into films on Petri dishes by drying at 60o C for 12 hours. Films with satisfactory texture were subjected to various physical tests. The mechanical properties of the films were assessed with Instron Universal Tester instrument (Model 3369) followed by folding endurance test. Ex-vivo mucoadhesive evaluation of the films was also conducted using Instron Probe Tack Tester (Model 5569).Results: All the films were brown and odourless. The plasticizer-free film (F1) was dry and brittle, while F4 - F6 remained wet and tacky. Films containing 1% and 2% v/v of PPG (F2) and (F3) respectively were smooth, flexible, hydrophillic in nature and exhibited pH dependent mucoadhesion and swelling properties in aqueous medium. Swelling index increased with increase in PPG concentration but reduced the mucoadhesive strength of the films.Conclusion: The CAG possessed good film-forming and mucoadhesive properties. It can be used as a coating agent for sustained release, pH dependent and mucoadhesive and topical drug delivery system.Keywords: Mucoadhesive, Plasticizers, Ex vivo, Film - formin

DYNAMICS OF RECTANGULAR ORTHOTROPIC PLATES USING CHARACTERISTIC ORTHOGONAL POLYNOMIAL – GALERKIN’S METHODS

The assumed deflection shapes used in the approximate methods such as in the Galerkin’s method were normally formulated by inspection and sometimes by trial and error, until recently, when a systematic method of constructing such a function in the form of Characteristic Orthogonal Polynomial (COPs) was developed by Bhat in 1985. In the vibrational analyses of orthotropic rectangular plates with different boundary conditions, the study used the characteristic orthogonal polynomial theory to obtain satisfactory approximate shape functions for these plates. These functions were applied to Galerkin indirect varational method to obtain new set of fundamental natural frequencies for these plates. The results were reasonable when compared with those in the previous work. All round simply supported thin rectangular plate (SSSS), rectangular clamped plated (CCCC) and rectangular plate with one edge clamped and all others edges simply supported (CSSS) gave 5.172, 9.429 and 6.202 natural frequencies in rad /sec respectively at 0.05%, 0.0% and 22.93% difference with the previous[3] results5.170rad/sec, 9.429rad/sec and 8.048rad/sec  for SSSS, CCCC and CSSS. For others like: rectangular plate with one edge simply supported and all other edges clamped (CCSC), rectangular plate simply supported at two opposite sides and clamped at the others (CSCS) and rectangular plate clamped at two adjacent sides and simply supported at the others (CCSS) with no available results, their natural frequencies obtained are 8.041rad/sec, 6.272rad/sec and 7.106rad/sec respectively. http://dx.doi.org/10.4314/njt.v36i1.

Mikrosfere s mukuna gumom za peroralnu primjenu glibenklamida: In vitro ispitivanje

An investigation into the suitability of mucuna gum microspheres for oral delivery of glibenclamide is presented. Mucuna gum microspheres were formulated under different conditions of polymer concentration and crosslinking time at constant speed. The formulated microspheres were thereafter loaded with glibenclamide by the remote loading process. The microspheres were evaluated according to particle size, yield, loading efficiency and swelling. In vitro release of glibenclamide from the microspheres was studied in simulated intestinal fluid (SIF, pH 7.4). The release data was fitted into two release models to investigate the mechanism of glibenclamide release from the microspheres. All the microspheres showed good swelling characteristics in distilled water. The investigation revealed that the microspheres produced with 5% (m/V) mucuna gum with a crosslinking time of 5 h had the optimum prolonged release pattern. The microspheres produced using 10% (m/V) mucuna gum with a crosslinking time of 1 h had the highest delayed release of the incorporated drug whereas those without crosslinking had the fastest release of the incorporated active ingredient. Ritger-Peppas case I transport model appeared to have adequately described the release process as about 54% of the batches of microspheres conformed to this model. This implies that a formulation of glibenclamide-loaded mucuna gum microspheres is likely to offer a reliable means of delivering glibenclamide by the oral route.U radu je opisana priprava mikrosfera s mukuna gumom za peroralnu primjenu glibenklamida. Pri izradi mikrosfera varirana je koncentracija polimera i vrijeme umrežavanja, a brzina je bila konstantna. Mikrosfere su zatim punjene glibenklamidom metodom odvojenog punjenja. Pripravljenim mikrosferama procijenjena je veličina čestica, iskorištenje, učinkovitost punjenja (LE %) i sposobnost bubrenja. In vitro oslobađanje glibenklamida iz mikrosfera praćeno je u simuliranoj intestinalnoj tekućini (SIF, pH 7.4). Za određivanje mehanizma oslobađanja ispitana su dva modela. Sve mikrosfere su imale dobru sposobnost bubrenja u destiliranoj vodi. Optimalno produljeno oslobađanje glibenklamida postignuto je iz mikrosfera priređenih s 5% (m/V) mukuna gume, uz vrijeme umrežavanja 5 h. Ljekovita tvar se najsporije oslobađala iz mikrosfera priređenih s 10% (m/V) mukuna gume, uz vrijeme umrežavanja 1 h, dok se najbrže oslobađala iz mikrosfera s 10% (m/V) gume, bez umrežavanja. Nekoliko mehanizama oslobađanja uključeno je u otpuštanje ljekovite tvari iz mikrosfera. Međutim, Ritger-Peppasov transportni model I opisuje proces oslobađanja u 54% slučajeva, što znači da mikrosfere glibenklamida s mukuna gumom predstavljaju pouzdan sustav za peroralnu primjenu te ljekovite tvari

Examining Socio-Demographic Corelates of Land and Livestock Ownership Access Poverty in Nigeria Using the Core Welfare Indicator Questionnaire Survey Data

The aim of the study is to examine the socio-demographic variables that correlate with land and livestock ownership access poverty in Nigeria using the Core Welfare Indicator Questionnaire (CWIQ) survey data, a non-monetary welfare indicator survey. A composed sample of 77,400 (seventy-seven thousand, four hundred) housing units drawn from the 36 States and Federal Capital Territory-FCT was used for the study. Principal Component Analysis (PCA), Adapted-Foster Greer and Thorbecke, and binary logit model  were used to analyze the data. The PCA was used to derive the land and livestock ownership access poverty line. The study revealed that land access poverty incidence is high across all the geo-political zones in Nigeria although the northern geo-political zones have land access poverty below the national incidence while the southern geo-political zones have land access poverty incidence above national incidence region. Household size, polygamous marriage and gender more significantly increase poverty across the various indicators used while attaining post secondary school, living in an urban area significantly reduced poverty across the composite indicators used. The study recommends that beyond the institutional reform advocated by some researchers, there is the immediate policy needs therefore to address some socio-demographic issues in Nigeria as they concern access to land. Such critical issues include rural-urban dichotomy as well as the gender imbalance in access to land and livestock ownership. Key words: Socio-Demographic Correlates, Land and Livestock Access Povert

Psychiatric Morbidity among Subjects with Leprosy and Albinism in South East Nigeria: A Comparative Study

Background: Skin, which is the largest organ in the body, carries immense psychological significance. Disfiguring skin disorders may impact negatively on the mental health of individuals. Aim: This study compared the psychiatric morbidity of subjects with leprosy and albinism.Subjects and Methods: One hundred subjects with leprosy and 100 with albinism were interviewed. Sociodemographic questionnaire and General Health Questionnaire (GHQ.28) assessed the sociodemographic  characteristics and psychiatric morbidity, respectively. GHQ positive cases and 10% of noncases for each group were interviewed with Mini  International Neuropsychiatric Inventory for specific ICD.10 diagnoses.Results: Fifty.five percent (55/100) subjects with leprosy were GHQ positive cases while 41% (41/100) with albinism were GHQ positive cases. The risk of developing psychiatric morbidity was significantly higher in subjects with leprosy than in subjects with albinism (OR = 1.76, CI = 1.00 . 3.08, P = 0.04). The prevalence of specific psychiatric disorders among subjects with leprosy were depression 49% (49/100), generalized anxiety disorder (GAD) 18% (18/100), alcohol/drug abuse 16% (16/100), whereas in albinism depression was 51% (51/100), GAD 27% (27/100), and alcohol/drug abuse 7% (7/100). Male, married and uneducated subjects with leprosy had  significantly higher psychiatric morbidity than the male, married and  uneducated subjects with albinism, respectively. Conclusion: Psychiatric morbidity was higher in subjects with leprosy than in subjects with albinism. Male, married and uneducated subjects with leprosy significantly had higher morbidity than male, married and uneducated subjects with albinism respectively.Keywords: Albinism, Leprosy, Psychiatric morbidit

Evaluation of Immunomodulatory Effect of Immunace on Adjuvanticity of 1,2-Dioleoyl-3- trimethylammoniumpropane-based Liposomes

Purpose: To investigate the antibody effect of immunace on the adjuvanticity of 1,2-dioleoyl-3- trimethylammoniumpropane (DOTAP)- based liposomes.Method: The vesicles of the liposome-based ND vaccine were prepared by lipid film hydration method and physically characterized for shape, particle size and zeta potential. Forty experimental birds were divided into an unvaccinated group, a liposomal Newcastle disease (ND) vaccine group, combined liposomal ND vaccine and immunace group, and a live La Sota® vaccine group. The liposomal ND vaccine, liposomal ND vaccine and immunace and a live La Sota® vaccine groups were vaccinated orally at 3 and 6 weeks of age. Haemagglutination inhibition test was carried out after primary and booster doses.Results: The log2 mean antibody titre induced by the liposomal ND vaccine after secondary immunization of the birds was 9.60 ± 0.95 while that of the combined liposomal ND vaccine and immunace group was 7.00 ±1.71, and that of the live La Sota vaccine® was 6.00 ±0.63. There was no detectable antibody in the unvaccinated group throughout the experiment. At p < 0.05, the liposomal ND vaccine group, after secondary immunization, produced antibodies which were significantly higher than those of the combined immunace-liposomal ND vaccine group.Conclusion: There was a boost in the immune response of the birds immunized with liposomal ND vaccine and immunace after primary immunization only.Keywords: Antibody, Newcastle disease vaccine, La Sota, DOTAP, Immunace, Immunity, Adjuvan

Solidified Reverse Micellar Solution (SRMS)-Based Indomethacin Sustained-Release Tablets: Formulation and In vitro Evaluation

Purpose: To formulate and evaluate sustained-release indomethacin tablets based on solidified reverse micellar solution (SRMS).Methods: SRMS consisting of mixtures of phospholipid (Phospholipon® 90H) and triglyceride (Softisan® 154) were prepared in the ratios of 1:1, 2:1 and 1:2, respectively. SRMS-based tablets containing 75 mg of indomethacin each were prepared using a validated plastic mould. The physicochemical properties of the tablet formulations were studied. In vitro release study was carried out in simulated intestinal fluid (SIF, pH 7.5).Results: The results showed that the physicochemical properties of the tablet formulations were significantly affected by the composition/ratio of the lipid matrix used (p < 0.05). Tablet hardness ranged from 5.00 ± 0.39 to 5.60 ± 0.36 kgf for tablets formulated with SRMS 1:2 and 2:1 (N3 and N2), respectively. The tablets exhibited friability of < 1 % (p < 0.05). Erosion time in SIF ranged from 124.0 ± 0.5 to 180.0 ± 1.1 min while drug release from the tablets reached a maximum in 8 – 11 h for all thebatches.Conclusion: Indomethacin tablets based on SRMS exhibited good sustained-release properties and can be further developed to achieve once daily administration for improved patient adherence to therapy.Keywords: Solidified reverse micellar solution, Phospholipid, Triglyceride, Indomethacin, Sustained release

ORAL GENTAMICIN PREPARATION USING SOLIDIFIED LIPID PARTICULATE DELIVERY SYSTEM

Objective: Despite the broad pharmacological activity of gentamicin against a number of bacteria, it's very inadequate oral bioavailability due to poor intestinal membrane permeability has limited its formulation into oral dosage delivery system. This work was thus aimed at formulation and evaluation of gentamicin-loaded microemulsions based on preparation of lipid matrix for sustained release delivery.Methods: Oral gentamicin suspensions were prepared by emulsification method using Tween 80 as a mobile surfactant in the lipid matrix dispersion. The resultant oral suspensions were evaluated for mean particle size and morphology using a photomicrograph, encapsulation efficiency/entrapment, EE (%), dispersibility, pH and absolute drug content. Release study as a function of inhibition zone diameter (IZD) and in vitro release study was also carried out. The in vitro release study was performed in both simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.2) respectively. The release data were analyzed mathematically according to zero order, first order and Higuchi equations.Results: The prepared suspensions were cream-white in colour, easily dispersed and well homogenized. Batch D, which had least amount of excipients incorporated into the lipid matrix showed clumped irregular-shaped and less free-flowing particles. The particle size was significantly influenced by lipid matrix combination ratio in the presence of a surfactant (p<0.05). The mean particle size diameters of the samples were 15.44 mm, 10.64 mm, 4.12 mm, and 2.70 mm for batches A, B, C and D respectively. The values of EE obtained varied between 47% and 59% with Batch B exhibiting the highest value. The Higuchi model gave the best release kinetics result followed by zero order kinetics.Conclusion: Oral gentamicin prepared exhibited antibacterial properties against Klebsiella spp., Escherchia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa. The results suggest that a lipid matrix system could be useful as a sustained release oral delivery system of a poorly absorbable drug such as gentamicin