Formulation and Optimization of Sustained Release Matrix Tablet of Metformin HCl 500 mg Using Response Surface Methodology

Mandal, Uttam Kumar; Gowda, Veeran; Ghosh, Animesh; Selvan, S. Sindhanai; Solomon, Sam; Pal, Tapan Kumar

doi:10.1248/yakushi.127.1281

Cited by 48 publications

(36 citation statements)

References 23 publications

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“…Using a 5% significance level, a model is considered significant if the P-value (significance probability value) is less than 0.05. 27 Most of the terms in Table 4, including the individual model, were found to be significant (P0.05), except for a few terms (shown in bold). A positive coefficient effect of independent factors on entrapment efficiency (Y 1 )…”

Section: Mathematical Modelling For Rsm Optimizationmentioning

confidence: 98%

Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

Mahmood¹,

Taher²,

Mandal³

2014

IJN

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Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon ® 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a homogeneous distribution and low polydispersity index (0.08). They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 μg/cm 2 /hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser scanning microscopy proved an enhanced permeation of coumarin-6-loaded transfersomes, to a depth of approximately160 μM, as compared with rigid liposomes. These ex vivo findings proved that a raloxifene hydrochloride-loaded transfersome formulation could be a superior alternative to oral delivery of the drug.

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Section: Mathematical Modelling For Rsm Optimizationmentioning

confidence: 98%

Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

Mahmood¹,

Taher²,

Mandal³

2014

IJN

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“…Twodimensional contour and three-dimensional surface plots were also drawn for each response variable, depending on the respective polynomial model. These plots served as a very good tool for analyzing the interaction effects of the studied dependent variables (Shah et al, 2009;Mandal et al, 2007).…”

Section: Optimization Of Statistical Data Analysismentioning

confidence: 99%

Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology

Khalid¹,

Ahmad²,

Minhas³

et al. 2014

Braz. J. Pharm. Sci.

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The objective of the current study was to formulate mucoadhesive controlled release matrix tablets of flurbiprofen and to optimize its drug release profile and bioadhesion using response surface methodology. Tablets were prepared via a direct compression technique and evaluated for in vitro dissolution parameters and bioadhesive strength. A central composite design for two factors at five levels each was employed for the study. Carbopol 934 and sodium carboxymethylcellulose were taken as independent variables. Fourier transform infrared (FTIR) spectroscopy studies were performed to observe the stability of the drug during direct compression and to check for a drug-polymer interaction. Various kinetic models were applied to evaluate drug release from the polymers. Contour and response surface plots were also drawn to portray the relationship between the independent and response variables. Mucoadhesive tablets of flurbiprofen exhibited non-Fickian drug release kinetics extending towards zero-order, with some formulations (F3, F8, and F9) reaching super case II transport, as the value of the release rate exponent (n) varied between 0.584 and 1.104. Polynomial mathematical models, generated for various response variables, were found to be statistically significant (P<0.05). The study also helped to find the drug's optimum formulation with excellent bioadhesive strength. Suitable combinations of two polymers provided adequate release profile, while carbopol 934 produced more bioadhesion.Uniterms: Flurbifrofen/mucoadhesive controlled release tablets/formulation. Flurbifrofen/mucoadhesive controlled release tablets/in vitro evaluation. Drugs/release profile. Drugs/bioadhesion. Tablets/direct compression.O objetivo do presente estudo foi formular comprimidos mucoadesivos de flurbiprofeno, de liberação controlada, e otimizar o perfil da liberação do fármaco e a bioadesão, utilizando a metodologia de superfície de resposta. Prepararam-se os comprimidos via técnica de compressão direta, que foram avaliados in vitro quanto aos parâmetros de dissolução e da força bioadesiva. Planejamento com componente central para dois fatores em cinco níveis cada foi empregado para esse estudo. Carbopol 934 e carboximetilcelulose sódica foram tomados como variáveis independentes. Efetuaram-se estudos de espectroscopia por transformada de Fourier (FTIR) para observar a estabilidade do fármaco durante a compressão direta e para avaliar a interação a fármaco-polímero. Aplicaram-se vários métodos cinéticos para avaliar a liberação do fármaco dos polímeros. Gráficos de superfície de contorno e de resposta foram efetuados para retratar a relação entre as variáveis dependentes e a resposta. Os comprimidos mucoadesivos de flurbiprofeno apresentaram cinética de liberação não-fickiana, estendendo para ordem zero, para algumas formulações (F3, F8 e F9), alcançando transporte super caso II, à medida que o valor do expoente (n) de taxa de liberação variou entre 0,584 e 1,104. Modelos matemáticos polinomiais, gerados por diversas variáveis de resposta, ...

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“…However, formulations with low levels of polymer concentrations could cause an inconstant release and initial burst of the drug. [8] Hydroxypropyl methyl cellulose (HPMC) is a synthetic derivative of cellulose and a widely used polymer in the production of sustained release matrix tablets due to its rapid hydration, good compression, gelling characteristics and very low toxicity. [9] There has been a link established between the retarding effects of HPMC to the gelatinous layer formed when the polymer is hydrated by water.…”

Section: Introductionmentioning

confidence: 99%

Psyllium: a promising polymer for sustained release formulations in combination with HPMC polymers

Kaialy

Emami

Asare-Addo

et al. 2013

Pharmaceutical Development and Technology

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Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipient in the preparation of controlled release systems. Various formulations were prepared using theophylline as a model drug and investigated with view to achieve an ideal slow drug release profile. The addition of HPMC to psyllium significantly reduced burst release however the percentage of drug release within a 12 h period was too slow and thereby inadequate. This was overcome by the addition of lactose as hydrophilic filler which enabled a slow release with roughly 80% drug release in 12 h. The inclusion of HPMC within psyllium formulations changed the drug release kinetics from Fickian diffusion to anomalous transport. Granulated formulations demonstrated slower drug release than ungranulated or physical mixture and caused a change in dissolution kinetics from Fickian diffusion to anomalous transport. Milled granules showed more efficient controlled drug release with no burst release. Milling of the granules also changed the drug release kinetics to anomalous transport. Although, psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release.

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Formulation and Optimization of Sustained Release Matrix Tablet of Metformin HCl 500 mg Using Response Surface Methodology

Cited by 48 publications

References 23 publications

Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology

Psyllium: a promising polymer for sustained release formulations in combination with HPMC polymers

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