The Solubility–Permeability Interplay and Its Implications in Formulation Design and Development for Poorly Soluble Drugs

Dahan, Arik; Miller, Jonathan M.

doi:10.1208/s12248-012-9337-6

Cited by 241 publications

(142 citation statements)

References 48 publications

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“…26,[40][41][42][43][44] The solubility-permeability interplay cannot be ignored when using solubility-enabling formulations. 45,46 As mentioned earlier, we can draw a conclusion that increasing drug solubility utilizing pharmaceutical techniques does not necessarily lead to improved bioavailability.…”

Section: Pharmacokinetic Studymentioning

confidence: 86%

Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

Li¹,

Pan²,

Cui³

et al. 2016

IJN

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The objective of this work was to prepare an oil/water glimepiride (GM) microemulsion (ME) for oral administration to improve its solubility and enhance its bioavailability. Based on a solubility study, pseudoternary phase diagrams, and Box–Behnken design, the oil/water GMME formulation was optimized and prepared. GMME was characterized by dynamic laser light scattering, zeta potential, transmission electron microscopy, and viscosity. The in vitro drug release, storage stability, pharmacodynamics, and pharmacokinetics of GMME were investigated. The optimized GMME was composed of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol (cosurfactant), and increased GM solubility up to 544.6±4.91 µg/mL. The GMME was spherical in shape. The particle size and its polydispersity index were 38.9±17.46 nm and 0.266±0.057, respectively. Meanwhile, the GMME was physicochemically stable at 4°C for at least 3 months. The short-term efficacy in diabetic mice provided the proof that blood glucose had a consistent and significant reduction at a dose of 375 µg/kg whether via IP injection or IG administration of GMME. Compared with the glimepiride suspensions or glimepiride-meglumine complex solution, the pharmacokinetics of GMME in Wistar rats via IG administration exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability. There was a good correlation of GMME between the in vitro release values and the in vivo oral absorption. ME could be an effective oral drug delivery system to improve bioavailability of GM.

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Section: Pharmacokinetic Studymentioning

confidence: 86%

Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

Li¹,

Pan²,

Cui³

et al. 2016

IJN

View full text Add to dashboard Cite

show abstract

“…The bile salt concentration and the amount of lecithin, primarily phosphatidylcholine, are known to be important factors in the intestinal fluid affecting the drugs' solubility as well as permeability (Dahan and Miller, 2012;Jantratid et al, 2008). The intestinal solubility remains as one of the most important parameters in order to achieve the desired systemic drug concentration.…”

Section: Influence Of Fassif and Fessif On Permeability Of Drugsmentioning

confidence: 99%

“…Due to the high bile salt concentration, FeSSIF is reported to often lead to decreased apparent permeability of drugs (Dahan and Miller, 2012;Jantratid et al, 2008;Miller et al, 2011). Another factor that may influence the apparent permeability of the drug compounds is the relation between the drugs pKa values and the pH of the different media.…”

Section: Influence Of Fassif and Fessif On Permeability Of Drugsmentioning

confidence: 99%

“…It is known that drugs from different classes might be affected differently in the presence of biorelevant fluids and also the presence of certain components in the GI fluid such as lecithin and bile salt (sodium taurocholate) might have a large impact on the solubility and permeability of poorly soluble compounds (Bergstrom et al, 2014;Dahan and Miller, 2012). Among the biorelevant media, FaSSIF and FeSSIF, first introduced in 1998 by Dressman and co-workers and later modified to better predict in vivo behavior of drugs, are the most utilized fluids originally applied as dissolution medium and later employed as medium in the permeability screening (Galia et al, 1998;Jantratid et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Biomimetic PVPA in vitro model for estimation of the intestinal drug permeability using fasted and fed state simulated intestinal fluids

Naderkhani

Vasskog

Flaten

2015

European Journal of Pharmaceutical Sciences

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“…In the literature, there are different methods to enhance MA solubility and dissolution rate. The most commonly used techniques are the formation of inclusion complexes with several cyclodextrin derivatives (8)(9)(10) and preparation of solid dispersions (SD) with water soluble polymers (polyvinylpyrrolidone, PVP, or polyethylene glycol, PEG) (11) in binary and ternary systems with a disintegrant and Polysorbate 20, respectively (12). Solubility increase was achieved in both cases according to literature data, but there is no information regarding the effect of auxiliary substances on permeability.…”

mentioning

confidence: 99%

Preparation and investigation of mefenamic acid – polyethylene glycol – sucrose ester solid dispersions

et al. 2015

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Preparation and investigation of mefenamic acidpolyethylene glycol -sucrose ester solid dispersionsMefenamic acid (MA) is a widely used non-steroidal antiinflammatory (NSAID) drug. The adverse effects typical of NSAIDs are also present in the case of MA, partly due to its low water solubility. The aim of this study was to increase the water solubility of MA in order to influence its absorption and bioavailability. Solid dispersions of MA were prepared by the melting method using polyethylene glycol 6000 and different types (laurate, D-1216; palmitate, P-1670; stearate, S-1670) and amounts of sucrose esters as carriers. The X-ray diffraction results show that MA crystals were not present in the products. Dissolution tests carried out in artificial intestinal juice showed that the product containing 10 % D-1216 increased water solubility about 3 times. The apparent permeability coefficient of MA across human Caco-2 intestinal epithelial cell layers was high and, despite the difference in solubility, there was no further increase in drug penetration in the presence of the applied additives.Keywords: mefenamic acid, sucrose esters, PEG 6000, solid dispersion, Caco-2 cells Mefenamic acid [MA, 2-(2,3-dimethylphenyl)aminobenzoic acid], an anthranilic acid derivative, is a widely used non-steroidal anti-inflammatory (NSAID) drug (1).Regarding the pharmacokinetics of the drug, MA is absorbed from the small intestine (2), its bioavailability is about 90 % but is influenced by the amount of water ingested with the drug in fasting subjects. The t max is attained in 2-4 hours, and steady-state concentration is reached in 2-3 days (2, 3).Like other NSAIDs, MA can cause serious gastrointestinal adverse effects (bleeding, ulceration) due to its mechanism of action (4) and acting as an irritant of the gastrointestinal mucosa (5).MA belongs to class II of the biopharmaceutical classification system (BCS) -drugs with low solubility and high permeability; therefore, its oral bioavailability is determined by its dissolution rate in the gastrointestinal fluid and, consequently, it has variable absorp-

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The Solubility–Permeability Interplay and Its Implications in Formulation Design and Development for Poorly Soluble Drugs

Cited by 241 publications

References 48 publications

Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

Biomimetic PVPA in vitro model for estimation of the intestinal drug permeability using fasted and fed state simulated intestinal fluids

Preparation and investigation of mefenamic acid – polyethylene glycol – sucrose ester solid dispersions

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