Physicochemical considerations in the preparation of amorphous ritonavir–poly(ethylene glycol) 8000 solid dispersions

Law, Devalina; Krill, Steven L.; Schmitt, Eric A.; Fort, James J.; Qiu, Yihong; Wang, Weili; Porter, William R.

doi:10.1002/jps.1054

Cited by 170 publications

(115 citation statements)

References 26 publications

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“…2c). Similar observations have been made previously with drugs like ritonavir and carvedilol wherein amorphous forms exhibited incomplete release in comparison with the crystalline form; however, generation of SD improved the dissolution rate (10,11). Higher apparent solubility of amorphous IBS at all pH values and a higher intrinsic dissolution rate (6) suggested that IBS could be a good candidate for dissolution rate improvement through SD formation.…”

Section: Resultssupporting

confidence: 84%

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Improved dissolution of a poorly water soluble drug in solid dispersions with polymeric and non-polymeric hydrophilic additives

Chawla¹,

Bansal²

2008

Acta Pharmaceutica

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Aqueous solubility of a drug can be a critical limitation to its oral absorption. Lipophilic molecules, especially those belonging to the biopharmaceutics classification system (BCS) class II and IV, dissolve slowly, poorly and irregularly, and hence pose serious delivery challenges, like incomplete release from the dosage form, poor bioavailability, increased food effect, and high inter-patient variability (1). Many solubilization techniques have been described that either change the nature of the solvent environment (co- Irbesartan (IBS) is a hydrophobic drug with poor aqueous solubility and dissolution rate. Solid dispersions (SDs) of IBS were prepared with both small molecules (tartaric acid and mannitol) and polymeric additives (polyvinylpyrrolidone, PVP, and hydroxypropyl methylcellulose, HPMC). A 9.5 and 7 folds enhancement in solubility over the crystalline form (14.6 mg mL -1 ) was observed for tartaric acid (138 mg mL -1 ) and PVP (103 mg mL -1 ), respectively. Powder X-ray diffraction confirmed that IBS existed in the glassy state in all cases, even with excipients having low glass transition temperature. Thermal methods (differential scanning calorimetry and hot stage microscopy) were used to evaluate the miscibility of the drug and additives. These techniques suggested that tartaric acid led to generation of »amorphous solutions« in contrast to »amorphous suspensions« in other three cases.The in vitro dissolution of IBS depended on the additive load and increased with increasing concentration in the case of tartaric acid, an acidifying excipient. The results indicate the suitability of even small molecules for providing solubility benefits, which can be attributed to the good glass forming ability and reasonable ability of IBS to remain in the glassy state.

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Section: Resultssupporting

confidence: 84%

“…It was first confirmed that the method was specific for the analysis of IBS and additives did not interfere with the drug. In vitro dissolution studies of SDs were also performed using different concentrations of excipients, tartaric acid and PVP [10,20,40, 50, 60 and 80% (m/m)].…”

Section: In Vitro Dissolution Studiesmentioning

confidence: 99%

Improved dissolution of a poorly water soluble drug in solid dispersions with polymeric and non-polymeric hydrophilic additives

Chawla¹,

Bansal²

2008

Acta Pharmaceutica

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“…Samples (10-15 mg) were weighed and sealed into 40μL aluminium pans. DSC runs were conducted over a temperature range of 70 °C to 250 °C at a rate of 10 °C/minute in a nitrogen atmosphere (Law et al, 2001). …”

Section: Differential Scanning Calorimetrymentioning

confidence: 99%

“…A voltage of 40kV and a current of 30 mA for the generator were used, with Cu as the tube anode material. The solids were exposed to Cu-K α radiation (α1=1.54060 Å and α2=1.54439 Å, with a α1/α2 ratio of 0.5), over a range of 2θ angles from 10 °C to 30 °C, at an angular speed of 1 o (2θ) per minute (Law et al, 2001).…”

Section: X-ray Powder Diffractometrymentioning

confidence: 99%

Extended release promethazine HCl using acrylic polymers by freeze-drying and spray-drying techniques: formulation considerations

Tiwari

Srivastava

Tiwari³

et al. 2009

Braz. J. Pharm. Sci.

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The present study investigated a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RL100 and Eudragit S100 in different weight ratios (1:1 and 1: 5), and in combination (0.5+1.5), using freeze-drying and spray-drying techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM), as well as solubility and in vitro dissolution studies in 0.1 N HCl (pH 1.2), doubledistilled water and phosphate buffer (pH 7.4). Adsorption tests from drug solution to solid polymers were also performed. A selected solid dispersion system was developed into capsule dosage form and evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of spray-dried dispersions were related to increasing amount of polymers, while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RL100 had a greater adsorptive capacity than Eudragit S100, and thus its combination in (0.5+1.5) for S100 and RL 100 exhibited a higher dissolution rate with 97.14% drug release for twelve hours. Among different formulations, capsules prepared by combination of acrylic polymers using spray-drying (1:0.5 + 1.5) displayed extended release of drug for twelve hours with 96.87% release followed by zero order kinetics (r 2 = 0.9986).Uniterms: Promethazine hydrochloride/extended release. Drugs/extended release. Eudragit RL100. Eudragit S100. Acrylic polymers. Spray drying/pharmacotechnics. Freeze drying/pharmacotechnics. Extended realease/pharmacotechnics. Pharmaceutical formulations/evaluation. O presente trabalho compreendeu estudo de um novo sistema de liberação prolongada de cloridrato de prometazina (PHC) com polímeros acrílicos Eudragit RL100 e Eudragit S100 em diferentes proporções em massa (1:1 e 1:5) e em combinação (0,5+1,5), utilizando técnicas de liofilização e de secagem por aspersão As dispersões sólidas foram caracterizadas por espectrofotometria no infravermelho por transformada de Fourier (FT-IR), calorimetria diferencial de varredura (DSC), difratometria de raios X (PXRD), Ressonância Magnética Nuclear (RMN), microscopia eletrônica de varredura (SEM) e, também, por estudos de solubilidade e de dissolução in vitro em HCl 0,1 N (pH 1,2), água bidestilada e tampão fosfato (pH 7,4). Realizaram-se, também, testes de adsorção da solução do fármaco nos polímeros sólidos. Desenvolveu-se sistema de dispersão sólida exclusiva dentro das cápsulas, que foi avaliado por meio de estudos de dissolução in vitro. Relacionou-se o desaparecimento progressivo de picos do fármaco em perfis termotrópicos de dispersões secas por spray à quantidade aumentada de polímero, enquanto os estudos de SEM sugeriram dispersão homogênea do fármaco no polímero. O Eudragit RL100 apresentou maior capacidade de adsorção do que o Eudragit S100 e, dessa forma, a combinação de (0,5+1,5) para S100 ...

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“…It blocks the HIV protease, thereby reducing the viral load in the infected individual [10]. This drug is mainly suffers with low oral bioavailability due to degradation of RN by the cytochrome P450-3A4 (CYP3A4) isoenzymes in the distal intestine [11], efflux of the absorbed drug by counter transporter proteins (mainly P-glycoprotein) present in the distal intestine [12,13] and is unstable at alkaline pH [14]. It shows pH-dependent solubility and solution stability [15].…”

Section: Introductionmentioning

confidence: 99%

Development and Characterization of Gastroretentive Drug Delivery System for Ritonavir Tablets Using Natural Polymers

Chukka

Shaik

2017

Asian J Pharm Clin Res

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Objective: This study involves preparation and evaluation of floating tablets of ritonavir (RN) for improving the drug bioavailability by prolongation of gastric residence time. RN is an antiretroviral agent used in the treatment of HIV and viral diseases have been taken as a model drug in this investigation because of its low biological half-life (3-5 hrs). Moreover, it is primarily absorbed from stomach.Methods: RN floating tablets were prepared by the dry granulation technique, using guar gum and xanthan gum as polymers, sodium bicarbonate as effervescent agent, polyvinylpyrrolidone as binding agent, Dicalcium phosphate as diluents, crospovidone as swelling agent and magnesium stearate as lubricant. The prepared tablets were evaluated for various physicochemical parameters.Results: Drug-excipient interaction studies were conducted by Fourier transform infrared spectroscopy and differential scanning calorimetry. The results suggested that there was no incompatibility between the drug and polymers. The prepared tablets were evaluated for their physical characteristics. All the parameters were within the pharmacopoeial limits. Further, tablets were also studied for their floating properties and in vitro drug release characteristics. The tablets exhibited controlled and prolonged drug release profiles. The developed formulation was found to be stable. Conclusion:The developed floating tablets of RN exhibit prolonged release up to 12 hrs, and thus may improve bioavailability and minimize fluctuations in plasma drug concentrations.

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Physicochemical considerations in the preparation of amorphous ritonavir–poly(ethylene glycol) 8000 solid dispersions

Cited by 170 publications

References 26 publications

Improved dissolution of a poorly water soluble drug in solid dispersions with polymeric and non-polymeric hydrophilic additives

Improved dissolution of a poorly water soluble drug in solid dispersions with polymeric and non-polymeric hydrophilic additives

Extended release promethazine HCl using acrylic polymers by freeze-drying and spray-drying techniques: formulation considerations

Development and Characterization of Gastroretentive Drug Delivery System for Ritonavir Tablets Using Natural Polymers

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