Effect of Vehicle Amphiphilicity on the Dissolution and Bioavailability of a Poorly Water-Soluble Drug from Solid Dispersions

Serajuddin, Abu T.M.; Sheen, Pai‐Chang; Mufson, Daniel; Bernstein, David F.; Augustine, Matthew A.

doi:10.1002/jps.2600770512

Cited by 155 publications

(70 citation statements)

References 10 publications

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“…Combining several properties favorable to drug dissolution and intestinal absorption, these preparations successfully induced efficient absorption of drugs with different structures and pharmacological activities (8)(9)(10)(11). pH-sensitive particles provide a convenient alternative for administering high doses of drug without the limitations encountered with other formulations (eg, lipid-based or conventional solid dispersion systems, which frequently face manufacturing and stability problems) (4,6,7). In addition, the described particles have the advantage of being constituted of a material commonly used in conventional oral formulation.…”

Section: Resultsmentioning

confidence: 99%

“…Another strategy has relied on the obvious advantage of increasing the surface area available for dissolution of the drug, as illustrated by drug micronization (5) or microemulsification of lipid vehicles (4). A third strategy is based on the formulation of poorly water soluble drugs in solid dispersions (solid solution or dispersion of the drug in excess of its solubility in a water-soluble matrix) in which the drug is present as a polymorph, solvate, or amorphous form that may favor its dissolution (4)(5)(6)(7). However, so far, constraints of solubility, potential interaction of the drug with excipients, and physical stability limitations have restricted the use of such formulations (4-7).…”

Section: Introductionmentioning

confidence: 99%

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pH-Dependent dissolving nano- and microparticles for improved peroral delivery of a highly lipophilic compound in dogs

et al. 2001

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RR01, a new highly lipophilic drug showing extremely low water solubility and poor oral bioavailability, has been incorporated into pHdependent dissolving particles made of a poly(methacrylic acid-co-ethylacrylate) copolymer. The physicochemical properties of the particles were determined using laser-light-scattering techniques, scanning electron microscopy, highperformance liquid chromatography, and x-ray powder diffraction. Suspension of the free drug in a solution of hydroxypropylcellulose (reference formulation) and aqueous dispersions of pHsensitive RR01-loaded nanoparticles or microparticles were administered orally to Beagle dogs according to a 2-block Latin square design (n = 6). Plasma samples were obtained over the course of 48 hours and analyzed by gas chromatography/mass spectrometry. The administration of the reference formulation resulted in a particularly high interindividual variability of pharmacokinetic parameters, with low exposure to compound RR01 (AUC 0-48h of 6.5 μg.h/mL and coefficient of variation (CV) of 116%) and much higher T max , as compared to both pH-sensitive formulations. With respect to exposure and interindividual variability, nanoparticles were superior to microparticles (AUC 0-48h of 27.1 μg.h/mL versus 17.7 μg.h/mL with CV of 19% and 40%, respectively), indicating that the particle size may play an important role in the absorption of compound RR01. The performance of pH-sensitive particles is attributed to their ability to release the drug selectively in the upper part of the intestine in a molecular or amorphous form. In conclusion, pHdependent dissolving particles have a great potential as oral delivery systems for drugs with low water solubility and acceptable permeation properties.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

pH-Dependent dissolving nano- and microparticles for improved peroral delivery of a highly lipophilic compound in dogs

et al. 2001

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“…Sometimes the dissolution of poorly soluble drugs requires dissolution media that are different from those normally used for water-soluble drugs. One technique that is useful in the dissolution of such drugs is the incorporation of a small amount of surfactant in the dissolution medium (15,16). The use of surfactants in dissolution systems may be considered as physiologically meaningful because of the presence of natural surfactants such as bile salts and bile acids in the gastrointestinal tract (17).…”

Section: Dissolution Studiesmentioning

confidence: 99%

Development of a Discriminating Dissolution Method for Immediate-Release Soft Gelatin Capsules Containing a BCS Class II Compound

Damian¹,

Harati²,

Pathak³

et al. 2016

Dissolution Technol.

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The purpose of this study was to develop a robust dissolution procedure for liquid-filled, soft gelatin capsules (SGCs) that can distinguish small but real changes in drug product formulation. SGCs were manufactured using different ratios of fill formulations. The formulations were evaluated by performing dissolution testing on fresh capsules and capsules that were aged at different time points and conditions. USP Apparatus 1 (basket) and 2 (paddle) at rotating speeds of 50, 75, or 100 rpm were used to evaluate the release characteristics of the formulations. The model-independent method using difference factor (f1) and similarity factor (f2) was employed to compare dissolution profiles. Dissolution data showed that fill material characteristics played a major role in controlling the rate of dissolution of our drug products. The basket increased the discriminatory power of the dissolution process regardless of speed. We observed that the paddle rotation speed may impact discrimination power but not the ability of the method to discriminate. The basket was successful for the quality assessment and characterization of formulation changes of our drug products. Through understanding of drug product characteristics and evaluating parameters of dissolution testing, a methodology can be established to enable batch-to-batch evaluation.

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“…Gelucire44/14 has commonly been used in solid dispersion for the bioavailability enhancement of drugs. A commonly used surfactant, Polysorbate 80, when mixed with solid PEG, has also been reported to be an alternative surface-active carrier 67,68,69 .…”

Section: Direct Capsule Fillingmentioning

confidence: 99%

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2010

IJPSR

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The solubility behavior of drugs remains one of the most challenging aspects in the formulation development. Although there was a great interest in solid dispersion systems during the past four decades to increase solubility by improving dissolution rate and bioavailability of poorly soluble drugs; there commercial use has been very limited, primarily because of manufacturing difficulties and various stability problems. It can be carried out by reducing drug particle size to the absolute minimum, and hence improving drug wet-ability, bioavailability may be significantly improved. Solid dispersion of drugs was generally produced by melt or solvent evaporation methods. Recently, surfactants have been included to stabilize the formulations, thus avoiding drug recrystallization and potentiating their solubility. New manufacturing processes to obtain solid dispersions have also been developed to reduce the drawbacks of the initial process. In this review, it is intended to discuss the eminent approach to improve the solubility or the dissolution rate and recent revival has been discussed.

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Effect of Vehicle Amphiphilicity on the Dissolution and Bioavailability of a Poorly Water-Soluble Drug from Solid Dispersions

Cited by 155 publications

References 10 publications

pH-Dependent dissolving nano- and microparticles for improved peroral delivery of a highly lipophilic compound in dogs

pH-Dependent dissolving nano- and microparticles for improved peroral delivery of a highly lipophilic compound in dogs

Development of a Discriminating Dissolution Method for Immediate-Release Soft Gelatin Capsules Containing a BCS Class II Compound

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