Enhancement of Oral Bioavailability of Cilostazol by Forming its Inclusion Complexes

Patel, Samir; Rajput, Sadhana J.

doi:10.1208/s12249-009-9249-7

Cited by 51 publications

(24 citation statements)

References 21 publications

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“…The FTIR spectra of pure CIL (Fig. 5) represent six specific characteristic peaks as compiled in Table X, well correlated with the already reported for CIL (59). In particular, the aliphatic C=O stretching and N-H stretching of quinolinone can be good hydrogen bonding sites.…”

Section: Ftir Analysissupporting

confidence: 84%

A Systematic Approach to Design and Prepare Solid Dispersions of Poorly Water-Soluble Drug

Verma

Rudraraju²

2014

AAPS PharmSciTech

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The objective of the present study was to define a systematic approach to design and prepare solid dispersions of poorly water-soluble drug. The systematic approach can be defined in four phases. In the first phase, glass forming ability is assessed, and in the second phase, probable excipients are screened. The screened excipients are evaluated (third phase) for glass transition temperatures (Tg) and miscibility studies according to Florey-Huggins interaction parameter. The predicted excipients are used to prepare the solid dispersion and evaluated for Tg and any interactions using Fourier transfer infrared studies (fourth phase), and the findings are correlated with phase three predictions. For this investigation, cilostazol (CIL) was selected as model drug, which was classified as a poor glass former. As per the physical chemical properties of CIL, ten excipients, both polymeric and non-polymeric, were selected and screened. Out of these, povidone, copovidone, hypromellose and Eudragit EPO were found theoretically miscible with CIL. After going through phase 2 to phase 4, only povidone, copovidone and hypromellose were confirmed as polymer of choice for preparing the solid dispersion of CIL with a prediction of better physical solid-state stability on the basis of good miscibility between drug and carrier.

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Section: Ftir Analysissupporting

confidence: 84%

A Systematic Approach to Design and Prepare Solid Dispersions of Poorly Water-Soluble Drug

Verma

Rudraraju²

2014

AAPS PharmSciTech

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“…Inclusion efficiency was calculated using the formula. 16 Inclusion efficiency = (estimated % drug content/ theoretical % drug content) x 100…”

mentioning

confidence: 99%

Carvedilol-?-cyclodextrin Systems: Preparation, Characterization and in vitro Evaluation

Sharma¹,

Jain

2013

Dhaka Univ. J. Pharm. Sci

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ABSTRACT:The purpose of this study was to improve the solubility and dissolution rate of carvedilol by forming a complex with β-cyclodextrin. Phase solubility diagrams revealed increase in solubility of the drug upon cyclodextrin addition, showing A N type curve. Complexation of carvedilol was carried out with β-cyclodextrin by physical mixing, kneading and co-precipitation method. The prepared complexes and physical mixture were characterized by Fourier transform infra red spectroscopy, differential scanning calorimetry, powder X-ray diffractometry and inclusion efficiency. It was also observed that the complexes exhibit higher dissolution rates than the pure drug and physical mixture. Among all carvedilol-cyclodextrin complexes, inclusion complex (1:5) prepared by co-precipitation method showed better release.

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“…From the available literature and data from pharmacokinetic studies of CLZ, it is evident that CLZ has poor bioavailability, presumably due to high first‐pass metabolism. The high inter‐animal variability observed in the pharmacokinetics of CLZ may be due to large variations in the expression of gut CYP450 3A, P‐gp and poor solubility of CLZ .…”

Section: Discussionmentioning

confidence: 99%

Drug–drug interaction study to assess the effects of atorvastatin co‐administration on pharmacokinetics and anti‐thrombotic properties of cilostazol in male Wistar rats

Vats

Varanasi

Arla

et al. 2012

Biopharm & Drug Disp

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Cilostazol (CLZ) and atorvastatin (ATV) are often co-prescribed to treat conditions such as peripheral arterial disease. In the present study, the drug-drug interaction potential of multi-dose ATV co-administration with CLZ on both pharmacokinetics and the anti-thrombotic property of CLZ is demonstrated. The pharmacokinetic parameters of CLZ (6 mg/kg, twice daily) were determined in male Wistar rats after 7 days co-administration with ATV (5 mg/kg, once daily) in order to assess the interaction potential between CLZ and ATV on chronic treatment. In vitro metabolic inhibition and everted gut sac studies were conducted to elucidate the mechanism of this interaction. Pharmacodynamic drug-drug interaction was evaluated on anti-thrombotic models including time to occlusion, platelet aggregation and rat tail bleeding time. A validated LC-MS/MS method was employed simultaneously to quantify both ATV and CLZ in rat plasma matrix. A statistically significant increase in systemic exposure (Css(max) by ~1.75 fold; AUC by ~3.0 fold) to CLZ was observed in ATV pre-treated rats. In vitro metabolism studies using liver microsomes (RLM and HLM) demonstrated statistically significant inhibition of CLZ metabolism when co-incubated with ATV. No change in apparent permeability of CLZ was observed in the presence of ATV. Atorvastatin showed a significant delay in artery occlusion time without altering CLZ's bleeding time and platelet aggregation profile. Collectively the results of these studies provide metabolic insight into the nature of drug-drug interaction between the selected drugs. Co-administration with ATV influences the pharmacokinetics and anti-thrombotic property of CLZ. A thorough clinical investigation is required before extrapolation of data to humans.

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Enhancement of Oral Bioavailability of Cilostazol by Forming its Inclusion Complexes

Cited by 51 publications

References 21 publications

A Systematic Approach to Design and Prepare Solid Dispersions of Poorly Water-Soluble Drug

A Systematic Approach to Design and Prepare Solid Dispersions of Poorly Water-Soluble Drug

Carvedilol-?-cyclodextrin Systems: Preparation, Characterization and in vitro Evaluation

Drug–drug interaction study to assess the effects of atorvastatin co‐administration on pharmacokinetics and anti‐thrombotic properties of cilostazol in male Wistar rats

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