Factorial design in the feasibility of producing Microcel MC 101 pellets by extrusion/spheronization

Sonaglio, Diva; Bataille, Bernard; Ortigosa, Claude; Jacob, Mohan V.

doi:10.1016/0378-5173(94)00246-2

Cited by 53 publications

(23 citation statements)

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“…[9][10][11][12] In the build-up to the approach, significant factors and the range of each process variable must be predetermined. According to previous studies, [3][4][5] the polymer type, polymer/drug ratio, and incorporated water-soluble excipients are the most potent factors that influence drug release from sustained-release dosage forms.…”

Section: Resultsmentioning

confidence: 99%

“…For this purpose, a computer optimization technique, based on a response surface methodology (RSM) utilizing a polynomial equation and artificial neural networks (ANN) has been widely used. [9][10][11][12] The optimization procedure involved systematic formulation designs to minimize the number of trials and analyze the response surfaces in order to realize the effect of causal factors and to obtain the appropriate formulations with target goals and the acceptable component region as process control conditions in practical preparation. Therefore, the primary purpose of this study was to develop and optimize the propranolol extended release formulations with target release profiles using RSM and multiple response optimization utilizing a quadratic polynomial equation.…”

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confidence: 99%

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Optimization of Sustained-Release Propranolol Dosage form Using Factorial Design and Response Surface Methodology

Huang

Tsai

Yang

et al. 2004

Biological & Pharmaceutical Bulletin

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Hydrophilic gel-forming matrix tablets are extensively used for oral extended release dosage forms due to their simplicity, cost effectiveness, and reduction of the risk of systemic toxicity due to dose dumping.1,2) Furthermore, pHindependent drug release is preferable for oral extended release formulations, so drug release in the GI tracts is not affected by intra-and inter-subject variations in both gastric pH and GI transit time. Hydroxypropylmethylcellulose (HPMC) is a pH-independent material and the drug release rates from HPMC matrix formulations are generally independent of processing variables such as compaction pressure, drug particle size, and the incorporation of a lubricant. 3)Therefore, HPMC is widely used to prepare the extended release dosage forms of water-insoluble drugs such as promethazine and water-soluble drugs such as acetaminophen. [3][4][5] Propranolol, a non-selective beta-adrenergic blocking agent, has been widely used in the treatment of hypertension, angina pectoris, and many other cardiovascular disorders. It is highly lipophilic and is almost completely absorbed after oral administration. However, much of the drug is metabolized by the liver during its first passage through the portal circulation; on average, only about 30% reaches the systemic circulation. Its elimination half-life is also relatively short (about 2-6 h).6-8) Therefore, it was chosen as a model drug for preparation of the once-daily extended-release dosage form.In the development of an extended release dosage form, an important issue was to design an optimized pharmaceutical formulation with an appropriate dissolution rate in a short time period and minimum trials. For this purpose, a computer optimization technique, based on a response surface methodology (RSM) utilizing a polynomial equation and artificial neural networks (ANN) has been widely used. [9][10][11][12] The optimization procedure involved systematic formulation designs to minimize the number of trials and analyze the response surfaces in order to realize the effect of causal factors and to obtain the appropriate formulations with target goals and the acceptable component region as process control conditions in practical preparation. Therefore, the primary purpose of this study was to develop and optimize the propranolol extended release formulations with target release profiles using RSM and multiple response optimization utilizing a quadratic polynomial equation. The second aim of the study was to evaluate and demonstrate the usefulness of RSM with multiple response optimization technology in the development of extended-release dosage forms containing water-soluble drug. MATERIALS AND METHODS MaterialsPropranolol hydrochloride and p-hydroxybenzoate-butyl ester were purchased from TCI Co. (Japan). Hydroxypropylmethylcellulose (HPMC, viscosity 4000 grade) was obtained from Shin Etsu (Japan). Microcrystalline cellulose (Avicel) was purchased from Asahi Co. (Japan). All other chemicals and solvents were of analytical reagent grade.Preparation of Propranol...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Optimization of Sustained-Release Propranolol Dosage form Using Factorial Design and Response Surface Methodology

Huang

Tsai

Yang

et al. 2004

Biological & Pharmaceutical Bulletin

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“…Entretanto, a diminuição do diâmetro destes orifícios não mostra qualquer alteração na distribuição de tamanho das partículas. O aumento do diâmetro dos orifícios da rede de extrusão também pode acarretar aumento do volume aparente dos pellets (Sonaglio et al, 1995) e mostra grande influência na friabilidade e na razão de dissolução da substância ativa (Noché et al, 1994). Pinto et al (1992) analisaram o efeito do comprimento dos orifícios da rede mantendo-se fixo o diâmetro.…”

Section: Velocidade Temperatura E Rede De Extrusãounclassified

Obtenção de pellets por extrusão e esferonização farmacêutica: parte I. avaliação das variáveis tecnológicas e de formulação

Santos¹,

Veiga²,

Pina³

et al. 2004

Rev. Bras. Cienc. Farm.

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INTRODUÇÃOA administração oral de uma forma farmacêutica é a via mais usual, confortável e conveniente para a liberação de uma substância ativa no organismo.Dentre as diversas formas farmacêutica para a via oral em que os sistemas de liberação de uma substância ativa podem ser concebidos, os pellets têm despertado crescente interesse devido às diversas vantagens tecnológicas e terapêuticas apresentadas (Reynolds, 1970;Bechgaard, Hegermann Nielsen, 1978;Eskilson 1985;Dietrich, 1989). Salientam-se as suas ótimas propriedades de escoamento, devido, principalmente, à forma esférica, estreita distribuição de tamanho de partículas, superfície suscetível ao revestimento por película com interesse à proteção entérica ou à liberação controlada ou sustentada, incorporação de grande quantidade de substância ativa e de substâncias ativas incompatíveis numa mesma forma farmacêutica, grande dispersão no trato gastrintestinal e conseqüente redução da irritação do trato por fármacos gastro-irritantes e baixo risco de efeitos adversos por superdosagem.O processo de produção de pellets, denominado peletização, consiste na aglomeração de pós finos de substância ativa e excipientes em pequenas unidades esféricas, assim denominadas pellets. Estas unidades esféricas diferenciam-se do produto obtido no processo de granulação clássica não apenas no que respeita ao processo pelo qual são produzidas, mas também pelas características físicas apresentadas.O interesse pela utilização de pellets como forma farmacêutica remonta à segunda metade da década de 1940. Em 1952, a Smith Kline & French (SKF) lançou no mercado uma nova forma farmacêutica, o Spansule, que consistia em cápsulas cheias com pellets revestidos que dissolveriam a tempos diferentes. Os pellets eram produzidos por revestimento em camadas a partir de núcleos de açúcar por uma técnica até então não empregada na in-*Correspondência:

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“…The influence of process and formulation variables upon the quality (e.g., size, shape, drug release rate) of produced pellets has extensively been investigated (Bashaiwoldu et al, 2004;Hasznos et al, 1992;Hellén and Yliruusi, 1993;Hellén et al, 1993a;Hellén et al, 1993b;Newton et al, 1995;Sonaglio et al, 1995;Sousa et al, 1996;Vervaet and Remon, 1996;Wan et al, 1993). Due to the large amount of liquid in the granulated mass, the interaction with water can induce phase transformations altering the pharmaceutical and biopharmaceutical performance of the drug.…”

Section: Introductionmentioning

confidence: 99%

Real-time image-based investigation of spheronization and drying phenomena using different pellet formulations

Burggraeve¹,

Sandler²,

Heinämäki³

et al. 2011

European Journal of Pharmaceutical Sciences

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Extrusion-spheronization (ES) is a frequently used agglomeration process in the pharmaceutical industry to manufacture spherical solid units or pellets with a narrow size and shape distribution. In this study, photometric stereo imaging was applied in real-time during the final steps of the ES process, being spheronization and drying. In addition to the pellet size distribution of undispersed (wet) samples, the imaging technique captures visual information on pellet shape and surface brightness. Pellet samples were taken at 20 time points during spheronization and were imaged atline (during spheronization) and off-line (after spheronization). Particle size distributions and visual image information were both used to characterize the spheronization behaviour of different formulations. Next, particle size distributions and surface brightness values calculated from the atline obtained images during fluid bed drying of pellets were analysed. The particle size distribution and brightness value changes occurring during pellet drying were explained both by the reduction in residual moisture content and drug solid-state transition. Due to the rapidness of the technique with regard to sample preparation, sample measurement and the acquisition of results in combination with the possibility to measure undispersed (wet) samples, valuable information on spheronization and drying characteristics of different formulations was obtained in real-time. KeywordsPhotometric stereo imaging -extrusion-spheronization -fluid bed drying -particle size and shape (distribution) -brightness -visualization

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Factorial design in the feasibility of producing Microcel MC 101 pellets by extrusion/spheronization

Cited by 53 publications

References 5 publications

Optimization of Sustained-Release Propranolol Dosage form Using Factorial Design and Response Surface Methodology

Optimization of Sustained-Release Propranolol Dosage form Using Factorial Design and Response Surface Methodology

Obtenção de pellets por extrusão e esferonização farmacêutica: parte I. avaliação das variáveis tecnológicas e de formulação

Real-time image-based investigation of spheronization and drying phenomena using different pellet formulations

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