Multivariate optimization of formulation and process variables influencing physico-mechanical characteristics of site-specific release isoniazid pellets

Pund, Swati; Joshi, Amita; Vasu, Kamala K.; Nivsarkar, Manish; Shishoo, C. J.

doi:10.1016/j.ijpharm.2009.12.034

Cited by 28 publications

(17 citation statements)

References 33 publications

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“…The low magnitudes of the bias values indicated a reasonable agreement between the predicted and the experimental values. It also indicated the robustness and high degree of predictive power of the generated quantitative mathematical models [21][22][23] . From the results obtained, it could be concluded that the generated Eqns.…”

Section: Table 5: All Responses Y1 To Y3 Along With Percent Error Formentioning

confidence: 88%

Formulation and Development of Gastroretentive Dipyridamole Microspheres: Proof of Concept by In vitro-In vivo Assessment

Vanshiv¹,

Joshi²,

Aware³

2018

pharmaceutical-sciences

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Vanshiv, et al.: Gastroretentive Dipyridamole MicrospheresThe present research was aimed at development and optimization of dipyridamole gastroretentive microspheres. Gastro retention was achieved using swellable polymeric material such as hydroxypropyl methylcellulose K4M, ethyl cellulose as release retardant using solvent diffusion evaporation method. 3 2 factorial design was applied for the development of best optimized formulation. The design was developed by considering two independent variables, ethyl cellulose, and stirring speed. Their effect on drug release, entrapment efficiency, particle size was analysed using response surface methodology. Formulation B1 among all formulations tested was found to be the best as it demonstrated prolonged floating time, maximum entrapment efficiency and drug release in a controlled manner. Formulation B1 was characterized further for presence of residual solvent by gas chromatography/mass spectrometry and the result showed absence of residual solvent. Gastro retention was assessed using the in vivo gamma scintigraphy technique in albino rabbits and the results indicated prolonged gastric retention. Pharmacokinetic study comparing pure dipyridamole and dipyridamole microspheres was conducted and C max , T max and K el were estimated. In vitro-in vivo correlation was determined using Wagner-Nelson function. Pharmacokinetic study revealed improved bioavailability (30 %) as compared to pure dipyridamole. Good correlation was obtained with a regression coefficient of 0.9704. The in vivo gamma scintigraphy and pharmacokinetic studies confirmed gastric retention of the prepared dipyridamole floating microspheres. Accelerated stability studies indicated integrity of the developed formulations.

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Section: Table 5: All Responses Y1 To Y3 Along With Percent Error Formentioning

confidence: 88%

Formulation and Development of Gastroretentive Dipyridamole Microspheres: Proof of Concept by In vitro-In vivo Assessment

Vanshiv¹,

Joshi²,

Aware³

2018

pharmaceutical-sciences

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“…At least 20 pellets from the usable yield fraction of each formulation were evaluated for their diametrical crushing force using a tablet strength tester (Electrolab EH 01) [8].…”

Section: Mechanical Crushing Forcementioning

confidence: 99%

Enhancement of Bioavailability of Fenofibrate with Alpha Tocopherol and Phospholipids as Solubilizers

Indira¹

2012

JBB

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The purpose of this study was to investigate the effect of different solubilizers namely alpha tocopherol, soy phosphatidylcholine 70, Phospholipon 80H, and Phospholipon 90H on the bioavailability of sustained release fenofibrate pellets using fluid bed coating by applying Taguchi design to optimize the type and concentration of solubilizer at four levels namely 0.5%, 1%, 1.5%, and 2%. The pellets were prepared by loading the fenofibrate blended with other excipients onto the core sugar pellets with the aid of the binder solution. Taguchi experimental runs with alpha tocopherol 1% and Phospholipon 90H 2% (test) showed significant differences in in vitro dissolution behavior of drug compared to the pure drug. The pharmacokinetics of pure drug and test was evaluated in healthy male Wistar rats and found that t 1/2 was reduced significantly (4.36 and 4.02 hours) while AUC 0-t (32.14 ± 6.38 μg h/ml, 36.94 ± 6.2 μg h/ml), C max (8.7 ± 2.31 μg/ml, 9.8 ± 2.2 μg/ml) were improved markedly compared to the pure drug with t 1/2 (7.339314 ± 3.1 hours), AUC 0-t (11.89 ± 8.13 μg h/ml), and C max (5.137 ± 3.37 μg/ml). The extent of the mean plasma exposure of fenofibrate was 2.7 and 3.1 fold higher in animals treated with test. The ANOVA results revealed that type and concentration of solubilizer are crucial for enhancement of in vitro dissolution profile. Hence use of solubilizers may be the promising way to improve the oral bioavailability of fenofibrate. Enhancement of Bioavailability of MethodsDrug loading: Drug was loaded onto sugar spheres using fluidized bed processor . The sugar spheres were loaded into the fluidized bed processor and warmed for about 10 -15 minutes. Binder solution was prepared by dissolving Povidone K30 and sugar in purified water under constant stirring. Unmicronized fenofibrate which was pre blended and pulverized (0.5 mm screen pulverizer) with other excipients was incorporated intermittently into the solution under constant stirring. The obtained solution was loaded onto the circulating sugar spheres (800 μm). The wet spheres were dried simultaneously during the process of circulation in wurster chamber. The process was continued till the complete solution was consumed. The various processing variables namely inlet air temperature (40-45°C), outlet air temperature (30-33°C), product temperature (36-40°C), chamber humidity (58-60%), air flow (85 m 3 /hr), compressed air pressure (1.5-3.0 kg/cm 2 )The peristaltic pump rpm (10-35) and spray rate (2 ml/min) were optimized in the preliminary trials.Design of experiment to optimize drug loaded fenofibrate pellets: Taguchi L16 design of experiment was used to study the effect of two variables namely, type of solubilizer and concentration of solubilizer at four different levels as given in Table 1 and Table 2. All the experimental runs were analyzed using Minitab statistical software package (version 15). Characterization methodsInfrared Spectroscopy analysis of drug and excipients: FT-IR spectra were obtained using FT-IR spectrometer (Model Nic...

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“…In addition, graphical analysis by Lenth's method shows that changes of levels that are active on response correspond to bars that exceed the dotted vertical lines, which signify experimental error and give the important factors to be selected ( Figures 3A and 3B). [24][25][26] Bayesian analysis of coefficients was also carried out ( Figures 3C and 3D). This was an a posteriori calculation of the probability that each of the effects is active and is represented graphically as box plots.…”

Section: Factorial Designmentioning

confidence: 99%

Chronomodulated press-coated pulsatile therapeutic system for aceclofenac: optimization of factors influencing drug release and lag time

Patil¹,

Pund²,

Joshi³

et al. 2011

CPT

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Background:The objective of this study was to develop and evaluate a press-coated pulsatile drug delivery system intended for treatment of early morning stiffness and symptomatic relief from pain in patients with rheumatoid arthritis. Methods: The formulation involved press coating of a rupturable coat around a rapidly d isintegrating core tablet of aceclofenac. A three-factor, two-level, full factorial design was used to i nvestigate the influence of amount of glyceryl behenate, amount of sodium chloride in the coating c omposition, and the coating level on the responses, ie, lag time to release and amount of aceclofenac released in 450 minutes. Results: Glyceryl behenate and the coating level had a significant influence on lag time, while sodium chloride helped in the rupture of the coat by acting as a channeling agent. After the coat was ruptured, the core tablet showed a rapid release of aceclofenac due to the presence of Ac-Di-Sol ® . Graphical analysis of effects by Lenth's method and Bayesian analysis of coefficients enabled identification of variables active on the selected responses. The optimized formulation comprised 20% w/w glyceryl behenate and 2.2% w/w sodium chloride with a 650 mg coating level, and showed a desired lag time of 358.23 minutes, which mimics the fluctuating symptoms of rheumatoid arthritis, followed by rapid release of aceclofenac.

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Multivariate optimization of formulation and process variables influencing physico-mechanical characteristics of site-specific release isoniazid pellets

Cited by 28 publications

References 33 publications

Formulation and Development of Gastroretentive Dipyridamole Microspheres: Proof of Concept by In vitro-In vivo Assessment

Formulation and Development of Gastroretentive Dipyridamole Microspheres: Proof of Concept by In vitro-In vivo Assessment

Enhancement of Bioavailability of Fenofibrate with Alpha Tocopherol and Phospholipids as Solubilizers

Chronomodulated press-coated pulsatile therapeutic system for aceclofenac: optimization of factors influencing drug release and lag time

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