Michael A. Odeniyi

Evaluation of Cedrela gum as a binder and bioadhesive component in ibuprofen tablet formulations

Propriedades de compressao, mecânicas e de formulacoes de comprimidos bioadesivos, que incorporam nova goma de mascar obtidas a partir de incisao de tronco da arvore de Cedrela odorata, foram avaliadas e comparadas com aquelas contendo hidroxipropilmetilcelulose (HPMC). Propriedades de compressao foram avaliadas usando a razao de Hausner, indice de Carr, ângulo de repouso e os graficos de Heckel, Kawakita e Gurnham. Prepararam-se comprimidos de ibuprofeno utilizando o metodo de granulacao a umido. Realizaram-se estudos de bioadesividade utilizando o metodo de cilindro rotativo em tampao fosfato pH 6,8, ou meio acido com 0,1 M de acido cloridrico. A goma e um polimero de baixa viscosidade (48 cPs) e a espectroscopia no infravermelho por Transformada de Fourier (FTIR) revelou a presenca de um grupo hidroxila. Valores de Py e Pk, que sao medidas de plasticidade, mostraram que a goma e significativamente (p <0,05) mais plastica do que HPMC e que a plasticidade aumenta com a concentracao de polimero. Todas as formulacoes de comprimidos mostraram-se nao-friaveis (<1,0%) e aquelas contendo a goma apresentaram maior resistencia ao esmagamento (130.95N) do que aquelas contendo HPMC (117.85N) em 2,0% (p/p) do ligante. As formulacoes que incorporaram a goma eram nao-desintegrantes e apesentaram tempo de liberacao significativamente maior do que aquelas contendo HPMC. As formulacoes de goma de Cedrela aderiram a incisao de ileo de porco por tempo maior do que aquelas contendo HPMC com a maior concentracao de ligante. A goma Cedrela apresentou melhor fluxo, compressao e propriedades de ligacao do que HPMC e e adequada como bioadesivo e para a liberacao sustentada de farmacos.

Application of freeze-drying technology in manufacturing orally disintegrating films

Abstract Freeze drying technology has not been maximized and reported in manufacturing orally disintegrating films. The aim of this study was to explore the freeze drying technology in the formulation of sildenafil orally disintegrating films and compare the physical properties with heat-dried orally disintegrating film. Central composite design was used to investigate the effects of three factors, namely concentration of carbopol, wheat starch and polyethylene glycol 400 on the tensile strength and disintegration time of the film. Heat-dried films had higher tensile strength than films prepared using freeze-dried method. For folding endurance, freeze-dried films showed improved endurance than heat-dried films. Moreover, films prepared using freeze-dried methods were thicker and had faster disintegration time. Formulations with higher amount of carbopol and starch showed higher tensile strength and thickness whereas formulations with higher PEG 400 content showed better flexibility. Scanning electron microscopy showed that the freeze-dried films had more porous structure compared to the heat-dried film as a result of the release of water molecule from the frozen structure when it was subjected to freeze drying process. The sildenafil film was palatable. The dissolution profiles of freeze-dried and heat-dried films were similar to Viagra® with f2 of 51.04 and 65.98, respectively.

Influence of binder type and process parameters on the compression properties and microbial survival in diclofenac tablet formulations

The influence of binder type and process parameters on the compression properties and microbial survival in diclofenac tablet formulations were studied using a novel gum from Albizia zygia. Tablets were produced from diclofenac formulations containing corn starch, lactose and dicalcium phosphate. Formulations were analyzed using the Heckel and Kawakita plots. Determination of microbial viability in the formulations was done on the compressed tablets of both contaminated and uncontaminated tablets prepared from formulations. Direct compression imparted a higher plasticity on the materials than the wet granulation method. Tablets produced by wet granulation presented with a higher crushing strength than those produced by the direct compression method. Significantly higher microbial survival (p< 0.05) was obtained in formulations prepared by direct compression. The percent survival of Bacillus subtilis spores decreased with increase in binder concentration. The study showed that Albizia gum is capable of imparting higher plasticity on materials and exhibited a higher reduction of microbial contaminant in the formulations. The direct compression method produced tablets of reduced viability of microbial contaminant.

Formulation and Evaluation of Oral Dissolving Films of Amlodipine Besylate Using Blends of Starches With Hydroxypropyl Methyl Cellulose

BACKGROUND Natural polymers serve as cheap, non-toxic, biocompatible excipients in oral drug delivery. These advantages inform their uses in the design of drug dosage forms. OBJECTIVES The aim of the study was to prepare and evaluate oral dissolving films of amlodipine besylate, an anti-hypertensive drug, using starch/polymer blends. MATERIAL AND METHODS Bambara nut (BAM) and the African yam bean (AYB) starches were individually blended with hydroxypropyl methyl cellulose (HPMC). The material and rheological properties of the blends were determined. Amlodipine besylate was incorporated by dispersion and films were prepared by solvent evaporation method and evaluated for mechanical and drug release properties. RESULTS The BAM/HPMC blends had higher viscosity values than the corresponding AYB/HPMC blends. All the blends gave a Hausner ratio above 1.25 and Carrs index above 22. Blends of ratio 1 : 1 and 2 : 1 produced good films and were subsequently evaluated. All films disintegrated within 15 mins but had poor folding endurance. BAM/HPMC (1 : 1) and AYB/ /HPMC (2 : 1) released all of the drug content within 30 min. The ranking for dissolution profile was AYB/HPMC (2 :1 ) > BAM/ /HPMC (1 :1 ) > BAM/HPMC (2 : 1) > AYB/HPMC (1 : 1). The type and ratio of starch in the blend influenced the drug release pattern of the films. CONCLUSIONS Starch/HPMC blend ratios of 1 : 1 and 2 : 1 were found suitable for the formulation of oral dissolving film of amlodipine besylate with good disintegration time and drug release profile.

Effect of compression pressure on mechanical and release properties of tramadol matrix tablets

Abstract Drug delivery to the proper site of action in the body is greatly influenced by the excipients used and some processing variables such as changes in compression force. The aim of this investigation was to study the influence of changes in compression forces during tablet manufacturing on the mechanical and release properties of Tramadol matrix tablet. Hardness and friability were used as assessment parameters for mechanical properties while release properties were analysed using dissolution test. Data were analysed using One-way ANOVA at p < 0.05. Tablet hardness and friability were typically compression pressure-dependent with a significant difference in tablet hardness and friability with increase in compression pressure (p < 0.001). Drug release was best expressed by Korsmeyer-Peppas equation as the plots showed high linearity (r2) of 0.998 and 0.988 for formulations containing Xanthan gum and Sodium carboxymethylcellulose, respectively. Drug release from formulations containing Xanthan gum was mainly by diffusion while a combination of diffusion and chain relaxation was the mechanism of drug release from formulation containing Sodium Carboxymethylcellulose. The release properties of tramadol matrix tablet were not significantly influenced by compression pressure but rather by the polymer and the material properties of the drug.

Compressional, mechanical and release properties of a novel gum in paracetamol tablet formulations

ABSTRACT The binding properties of Eucalyptus gum obtained from the incised trunk of Eucalyptus tereticornis, were evaluated in paracetamol tablet formulations, in comparison with that of Gelatin B.P. In so doing, the compression properties were analyzed using density measurements and the compression equations of Heckel, Kawakita and Gurham. In our work, the mechanical properties of the tablets were assessed using the crushing strength and friability of the tablets, while the drug release properties of the tablets were assessed using disintegration and dissolution times. The results of the study reveal that tablet formulations incorporating Eucalyptus gum as binder, exhibited faster onset and higher amount of plastic deformation during compression than those containing gelatin. What is more, the Gurnham equation could be used as a substitute for the Kawakita equation in describing the compression properties of pharmaceutical tablets. Furthermore, the crushing strength, disintegration and dissolution times of the tablets increased with binder concentration, while friability values decreased. We noted that no significant differences in properties exist between formulations derived from the two binders (p > 0.05) exist. While tablets incorporating gelatin exhibited higher values for mechanical properties, Eucalyptus gum tablets had better balance between mechanical and release properties - as seen from the CSFR/Dt values. Tablets of good mechanical and release properties were prepared using Eucalyptus gum as a binder, and, therefore, it could serve as an alternative binder in producing tablets with good mechanical strength and fast drug release.

Evaluation of two novel plant gums for bioadhesive microsphere and sustained-release formulations of metformin hydrochloride

BACKGROUND The biological half life of metformin requires multiple doses which are associated with poor patient compliance. This justifies the need for a dosage form with reduced dosing frequency. OBJECTIVES Gums from Enterolobium cyclocarpum and Cedrela odorata trees were evaluated in formulating bioadhesive microspheres containing metformin hydrochloride, for sustained drug release. Hydroxylpropylmethyl cellulose (HPMC) was the standard. MATERIAL AND METHODS Microspheres were produced from formulations of API and either cedrela gum (FC), enterolobium gum (FE) or HPMC (FH), using a W/O solvent extraction technique. The microspheres were characterized using a particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffractometer (PXRD), drug entrapment, in vitro release and mucoadhesion studies. The data was analyzed using ANOVA and t-test at p = 0.05. RESULTS FT-IR spectroscopy indicated no alteration in the functional groups of metformin. A yield of 92-98% microspheres was obtained from all the formulations which had a particle size range of 72-84 μm. SEM revealed cylindrical to near-spherical particles with rough surfaces. The drug release profile showed a burst over the first 30 min followed by a steady release for about 5 h and a slow release for 5 days. Formulations containing the gums sustained the release of API for almost the same time as HPMC formulations; the ranking order was FE > FH > FC (p > 0.05). All the formulations exhibited good concentration-dependent mucoadhesive properties. CONCLUSIONS The gums were suitable for formulation of mucoadhesive microspheres for sustained release of metformin. The formulations showed good release properties in an alkaline pH.

Clinicopathological evaluation of Newcastle disease virus vaccination using gums from Cedrela odorata and Khaya senegalensis as delivery agents in challenged chickens

Abstract Following previous studies on delivery potential and immune response of chickens given Newcastle disease vaccine with gums, this study was conducted to evaluate the protective ability of vaccines delivered with plant gums against clinicopathological features of Newcastle disease (ND). Processed gums from incised trunks of Cedrela odorata and Khaya senegalensis trees were combined with ND vaccine in ratio 2:2:1 and administered at 21 days to white leghorn cockerels after weaning of maternal antibodies. The birds were grouped into gum-vaccine-oral (GVOR), vaccine-oral (VOR), gum-vaccine-ocular (GVOC), vaccine-ocular (VOC), gum-oral (GOR), gum-ocular (GOC), no-gum-no-vaccine/challenged (NGNV/C), no-gum-no-vaccine/unchallenged (NGNV/U). Vaccination was boosted with the same preparation at day 42 while birds were challenged with live ND virus (KUDU strain) at day 84. Clinical signs (Dullness, Diarrhoea, Paralysis, Torticollis) Post infection (Pi), terminal weakness, gross and histology lesions were scored on a severity scale from absent (0-), mild (1+) to moderate (2+) and severe (3+). Scores were assigned a quantitative score of 0, 10, 20, 30 respectively. Clinical signs scores for the 5 week Pi were subjected to Friedman test to assess the significance of severity among the groups. The test was significant at 1% significance level which implies that the clinical signs ranked highest in the NGNV/C, followed by the Gum alone groups, the vaccine alone groups and the gum-vaccine groups irrespective of route. Moribund birds subsequently euthanized were seen in the GOR and GOC group at 21% each and at 57% in NGNV/C group alone. No signs were seen in the NVNG/U group. Grossly, mild to moderate lesions were seen in all groups except GVOR and NGNV/U. At histology, pulmonary congestion, acute pneumonia, cecal tonsilar haemorrhages, gliosis and neuronophagia were present at different proportions in all groups except the GVOR and NGNV/U. Overall, lesion severity was least in the gum-vaccine groups while the oral groups had less lesion score compared to the ocular. From this study, phytogenic mucoadhesives polymers used hold immense potential as a delivery agent capable of improving protection against clinicopathologic features of Newcastle disease in previously vaccinated birds.

Material and Compression Properties of Cedrela odorata Gum Co-Processed with Plantain Starch and Microcrystalline Cellulose

BACKGROUND Many excipients used in tableting exhibit some undesirable properties such as poor flow, cohesion and lubricating characteristics, thus necessitating some modification to achieve the desired product. OBJECTIVES The objective of this study was to enhance the material, flow and compressional properties of Cedrela odorata gum (COG) (Family: Meliaceae) by co-processing with plantain starch (PS) and microcrystalline cellulose (MCC). MATERIAL AND METHODS The COG was co-processed with PS (or MCC) by physical co-grinding at ratio 1 : 1, 1 : 2 and 1 : 4, and characterized using morphological analysis, swelling index viscosity measurements, particle size analysis and FTIR spectra. The material, flow and compressional properties of the co-processed excipients were also evaluated. Results were analyzed using mean and standard deviation of data. RESULTS There was a decrease in the degree of agglomeration of COG and a reduction in the size of the powdered gum. The co-processed excipients were more spherical than the native excipients. The COG had the highest viscosity, while MCC and COG : PS (1 : 2) showed the highest and lowest degrees of swelling at 27.0 ± 0.05°C respectively. Water absorption capacity of the component excipients improved with co-processing COG : MCC increasing from 171.8 ± 1.54 (1 : 1) to 214.8 ± 1.07 (1 : 2), while COG : PS increased from 95.2 ± 0.08 (1 : 1) to 206.2 ± 0.13. There was a decrease in the percentage solubility of the co-processed excipients with the highest and lowest solubility observed in COG (54.1 ± 0.07%) and PS (3.7 ± 0.16%), respectively. The FTIR spectra indicate no significant interaction between the excipients. The poor flow of the component excipients did not improve with co-processing; however, there was a significant increase in compressibility. Generally, COG co-processed with MCC showed better compression properties when compared with COG co-processed with PS. CONCLUSIONS Co-processing of COD with MC or PS enhanced the characters of the component excipients, thus making the co-processed excipients suitable for direct compression of tablets without altering the chemical nature of the component excipients.

Powder properties of binary mixtures of chloroquine phosphate with lactose and dicalcium phosphate

A study was conducted on the packing and cohesive properties of chloroquine phosphate in binary mixtures with lactose and dicalcium phosphate powders. The maximum volume reduction due to packing as expressed by the Kawakita constant, a, and the angle of internal flow, θ, were the assessment parameters. The individual powders were characterized for their particle size and shape using an optical microscope. Binary mixtures of various proportions of chloroquine phosphate with lactose and dicalcium phosphate powders were prepared. The bulk and tapped densities, angles of repose and internal flow, as well as compressibility index of the materials were determined using appropriate parameters. The calculated and determined values of maximum volume reduction for the binary mixtures were found to differ significantly (P< 0.05), with the Kawakita plot being more reliable in determining the packing properties. Diluent type was found to influence the flow properties of the mixtures, with dicalcium phosphate giving predictable results while mixtures containing lactose were anomalous with respect to flow. The characterization of the packing and cohesive properties of the binary mixtures of chloroquine with lactose and dicalcium phosphate would be useful in the production of powders, tablets, capsules and other drug delivery systems containing these powders with desirable and predictable flow properties.