Solid state characteristics of ternary solid dispersions composed of PVP VA64, Myrj 52 and itraconazole

Wang, Xin; Michoel, Armand; Mooter, Guy Van den

doi:10.1016/j.ijpharm.2005.07.002

Cited by 87 publications

(37 citation statements)

References 13 publications

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“…To increase the bioavailability researchers formulated binary mixtures with various polymers creating either solid dispersions or solid solutions with enhanced dissolution rate [5,[8][9]. Solid dispersions containing ternary systems of the drug with polymers were also evaluated with successful increase in the dissolution of itraconazole [10][11][12]. Itraconazole dissolution was also enhanced by complexation with cyclodextrin derivatives or even by adsorption on ordered mesoporous silica .…”

Section: Introductionmentioning

confidence: 99%

Synergistic Enhancement of Itraconazole Dissolution by Ternary System Formation with Pluronic F68 and Hydroxypropylmethylcellulose

Maghraby

2009

Sci. Pharm.

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Pluronic F68 is a surfactant which can inhibit CYP3A4, an enzyme responsible for hepatic metabolism of many drugs including itraconazole. This study investigated the effect of incorporation of Pluronic F68 as a ternary component in solid dispersions of itraconazole with hydroxypropyl-methylcellulose (HPMC) on the dissolution rate of itraconazole. Binary solid dispersions with HPMC, reduced the drug crystallinity, increased the equilibrium solubility but showed slow dissolution. Binary dispersions with Pluronic produced eutectic systems but the increase in solubility and dissolution was lower than that of HPMC systems. Ternary system comprising optimum proportions of drug with Pluronic and HPMC enhanced the dissolution rate showing dissolution efficiency comparable to that obtained with the marketed product of itraconazole. The study thus presented a system capable of increasing the dissolution rate of itraconazole with a potential for increased oral bioavailability by inhibiting its pre-systemic metabolism as well.

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Section: Introductionmentioning

confidence: 99%

Synergistic Enhancement of Itraconazole Dissolution by Ternary System Formation with Pluronic F68 and Hydroxypropylmethylcellulose

Maghraby

2009

Sci. Pharm.

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“…ITR, classified as a BCS class II drug, has poor solubility in aqueous media (less than 0.001 mg mL -1 at 25 °C) (Shete et al, 2015) and has a dissolution rate limited poor oral bioavailability with pKa of 3.7 (Heykants et al, 1989) with due consideration of its relatively low Tg. Some investigations have reported formulation of solid dispersion systems (SDs) of crystalline ITR (CITR) (Jung et al, 1999;Verreck et al, 2003;Wang et al, 2005;Tao et al, 2009). However, till date, very less attention is paid towards preparing and stabilizing amorphous form of ITR (AITR) employing ternary SDs for improvement of its solubility.…”

Section: Introductionmentioning

confidence: 99%

Physical stabilization of amorphous itraconazole in solid dispersions for improved dissolution profile

Pore¹,

Shinde²,

Rao³

2016

J App Pharm Sci

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The main objective of the present investigation was to improve dissolution efficiency and stabilize amorphous form of itraconazole (ITR) through formulation of ternary solid dispersion system (SDs) with polyvinylpyrrolidone K30 (PVP K30) and sylysia ® 350 using spray drying technique. The prepared ternary SD system was characterized for solid state properties, in vitro dissolution efficiency and accelerated stability study at 40 °C/75% RH for the period of 3 months to explore extent of stabilization of amorphous itraconazole (AITR). Surprisingly, AITR was found to have no significant improvement in its dissolution characteristics compared to pure drug. The formation of cohesive supercooled liquid state might be the reason for poor solubility. Hence a combined approach of SD system with an antiplasticizing agent and surface adsorption technique was employed to prevail over functional inabilities of AITR. The binary and ternary SDs of AITR were prepared employing PVP K30 as antiplasticizer and/or sylysia ® 350 as adsorbent in the ratio 1:1:1 w/w using spray drying technique. The prepared systems have shown significant improvement in dissolution characteristics when compared to pure drug. Accelerated stability studies confirmed the absence of crystallization events over a period of 3 months endorsing excellent stabilization of AITR.

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“…The IR spectrum of ezetimibe (Figure 6Ca) was characterized by principal absorption peaks at 3,264.41, 2,913.81, 2,855.57, 1,879.87, 1,718.04, 1,602.50, 1,509.34, 1,445.82, 1,432.02, 1,354.03, 1,221.51, and 830.98 cm -1 . 32 Silicon dioxide (Figure 6Cb) and HPC (Figure 6Ce) showed their specific patterns. The physical mixture of solid SNEDDS (Figure 6Cc) and the physical mixture of the solid dispersions (Figure 6Cf) showed major peaks of ezetimibe.…”

mentioning

confidence: 96%

“…Thus, our results suggest that the drug existed in a crystalline and amorphous form in SMSD and SESD, respectively. 31,32 The PXRD profiles shown in Figure 6B were investigated for further verification of the internal physical state of the drug in these formulations. The drug (Figure 6Ba) showed a typical crystalline pattern, but carriers such as HPC (Figure 6Be) and silicon dioxide (Figure 6Bb) showed no peaks.…”

mentioning

confidence: 99%

“…The FTIR spectra of solid SNEDDS (Figure 6Cd), SMSD (Figure 6Cg), and SESD ( Figure 6Ch) showed that there was no shift in the drug peaks in these formulations, indicating that the drug and carriers had no chemical interactions in all formulations. [32][33][34] Among the prepared formulations, SESD showed more uniform behavior and a smaller particle size as compared with SMSD and solid SNEDDS (Figure 7). The ezetimibe powder did not show a uniform particle size distribution as compared with the formulations.…”

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confidence: 99%

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Comparative study on solid self-nanoemulsifying drug delivery and solid dispersion system for enhanced solubility and bioavailability of ezetimibe

Rashid¹,

Kim²,

Yousaf³

et al. 2015

IJN

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Background The objective of this study was to compare the physicochemical characteristics, solubility, dissolution, and oral bioavailability of an ezetimibe-loaded solid self-nanoemulsifying drug delivery system (SNEDDS), surface modified solid dispersion (SMSD), and solvent evaporated solid dispersion (SESD) to identify the best drug delivery system with the highest oral bioavailability. Methods For the liquid SNEDDS formulation, Capryol 90, Cremophor EL, and Tween 80 were selected as the oil, surfactant, and cosurfactant, respectively. The nanoemulsion-forming region was sketched using a pseudoternary phase diagram on the basis of reduced emulsion size. The optimized liquid SNEDDS was converted to solid SNEDDS by spray drying with silicon dioxide. Furthermore, SMSDs were prepared using the spray drying technique with various amounts of hydroxypropylcellulose and Tween 80, optimized on the basis of their drug solubility. The SESD formulation was prepared with the same composition of optimized SMSD. The aqueous solubility, dissolution, physicochemical properties, and pharmacokinetics of all of the formulations were investigated and compared with the drug powder. Results The drug existed in the crystalline form in SMSD, but was changed into an amorphous form in SNEDDS and SESD, giving particle sizes of approximately 24, 6, and 11 µm, respectively. All of these formulations significantly improved the aqueous solubility and dissolution in the order of solid SNEDDS ≥ SESD > SMSD, and showed a total higher plasma concentration than did the drug powder. Moreover, SESD gave a higher area under the drug concentration time curve from zero to infinity than did SNEDDS and SMSD, even if they were not significantly different, suggesting more improved oral bioavailability. Conclusion Among the various formulations tested in this study, the SESD system would be strongly recommended as a drug delivery system for the oral administration of ezetimibe with poor water solubility.

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Solid state characteristics of ternary solid dispersions composed of PVP VA64, Myrj 52 and itraconazole

Cited by 87 publications

References 13 publications

Synergistic Enhancement of Itraconazole Dissolution by Ternary System Formation with Pluronic F68 and Hydroxypropylmethylcellulose

Synergistic Enhancement of Itraconazole Dissolution by Ternary System Formation with Pluronic F68 and Hydroxypropylmethylcellulose

Physical stabilization of amorphous itraconazole in solid dispersions for improved dissolution profile

Comparative study on solid self-nanoemulsifying drug delivery and solid dispersion system for enhanced solubility and bioavailability of ezetimibe

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