Modeling the influence of cyclodextrins on oral absorption of low-solubility drugs: I. Model development

2010 ◽  
Vol 105 (2) ◽  
pp. 409-420 ◽  
Author(s):  
Ece Dilber Gamsiz ◽  
Lee Miller ◽  
Avinash G. Thombre ◽  
Imran Ahmed ◽  
Rebecca Lyn Carrier
Keyword(s):  
Oral Absorption ◽  
Model Development ◽  
Low Solubility ◽  
Low Solubility Drugs

Modeling the influence of cyclodextrins on oral absorption of low solubility drugs: II. Experimental validation

2010 ◽  
Vol 105 (2) ◽  
pp. 421-430 ◽  
Author(s):  
Ece Dilber Gamsiz ◽  
Lee Miller ◽  
Avinash G. Thombre ◽  
Imran Ahmed ◽  
Rebecca Lyn Carrier
Keyword(s):  
Experimental Validation ◽  
Oral Absorption ◽  
Low Solubility ◽  
Low Solubility Drugs

scholarly journals Prediction of Oral Absorption of Low-Solubility Drugs by Using Rat Simulated Gastrointestinal Fluids: The Importance of Regional Differences in Membrane Permeability and Solubility

2014 ◽  
Vol 17 (1) ◽  
pp. 106 ◽  
Author(s):  
Yusuke Tanaka ◽  
Toshiyuki Baba ◽  
Koji Tagawa ◽  
Ryoichi Waki ◽  
Shunji Nagata
Keyword(s):  
Oral Administration ◽  
Regional Differences ◽  
Oral Absorption ◽  
Aqueous Solubility ◽  
Oral Drug ◽  
Novel Approach ◽  
Low Solubility ◽  
Low Solubility Drugs ◽  
Saturated Solubility

Purpose. This study aimed to develop a novel approach for predicting the oral absorption of low-solubility drugs by considering regional differences in solubility and permeability within the gastrointestinal (GI) tract. Methods. Simulated GI fluids were prepared to reflect rat in vivo bile acid and phospholipid concentrations in the upper and lower small intestine. The saturated solubility and permeability of griseofulvin (GF) and albendazole (AZ), a drug with low aqueous solubility, were measured using these simulated fluids, and fraction absorbed (Fa) at time t after oral administration was calculated. Results. The saturated solubility of GF and AZ, a drug with low aqueous solubility, differed considerably between the simulated GI fluids. Large regional differences in drugs concentration were also observed following oral administration in vivo. The predicted Fa values using solubility and permeability data of the simulated GI fluid were found to correspond closely to the in vivo data. Conclusion. These results indicated the importance of evaluating regional differences in drug solubility and permeability in order to predict oral absorption of low-solubility drugs accurately. The new methodology developed in the present study could be useful for new oral drug development. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Prediction Characteristics of Oral Absorption Simulation Software Evaluated Using Structurally Diverse Low-Solubility Drugs

2020 ◽  
Vol 109 (3) ◽  
pp. 1403-1416 ◽  
Author(s):  
Naoya Matsumura ◽  
Shun Hayashi ◽  
Yoshiyuki Akiyama ◽  
Asami Ono ◽  
Satoko Funaki ◽  
...  
Keyword(s):  
Oral Absorption ◽  
Simulation Software ◽  
Low Solubility ◽  
Low Solubility Drugs

Powder Dissolution Method for Estimating Rotating Disk Intrinsic Dissolution Rates of Low Solubility Drugs

2009 ◽  
Vol 26 (9) ◽  
pp. 2093-2100 ◽  
Author(s):  
Konstantin Tsinman ◽  
Alex Avdeef ◽  
Oksana Tsinman ◽  
Dmytro Voloboy
Keyword(s):  
Rotating Disk ◽  
Dissolution Rates ◽  
Intrinsic Dissolution ◽  
Dissolution Method ◽  
Low Solubility ◽  
Low Solubility Drugs

Nasal Spray Device for Administration of Two-Part Drug Formulations

2019 ◽  
Author(s):  
Davin Rautiola ◽  
Ronald A. Siegel
Keyword(s):  
Nasal Spray ◽  
Drug Formulation ◽  
Spray Cone ◽  
Dose Administration ◽  
Single Action ◽  
Primary Breakup ◽  
Stability Issues ◽  
Low Solubility ◽  
Low Solubility Drugs ◽  
Pass Metabolism

Intranasal drug delivery is an attractive route to noninvasively achieve a rapid therapeutic effect, avoid first pass metabolism, and bypass the blood brain barrier. However, the types of drugs that can be administered by this route has been limited, in part, by device technology. Herein, we describe a pneumatic nasal spray device that is capable of mixing liquid and solid components of a drug formulation as part of the actuation process during dose administration. The ability to store a nasal spray drug formulation as two separate components can be leveraged to solve a variety of stability issues that would otherwise preclude intranasal administration. Examples of drugs that could be delivered intranasally by utilizing this two-part formulation strategy include biomolecules that are unstable in solution and low solubility drugs that can be rendered into metastable supersaturated solutions. A proof of concept nasal spray device prototype was constructed to demonstrate that a liquid and solid can be rapidly mixed and atomized into a spray in a single action. The primary breakup distance and angle of the spray cone were measured as a function of the function of the propellant gas pressure.

scholarly journals The BioGIT System: a Valuable In Vitro Tool to Assess the Impact of Dose and Formulation on Early Exposure to Low Solubility Drugs After Oral Administration

2018 ◽  
Vol 20 (4) ◽  
Author(s):  
Alexandros Kourentas ◽  
Maria Vertzoni ◽  
Vicky Barmpatsalou ◽  
Patrick Augustijns ◽  
Stefania Beato ◽  
...  
Keyword(s):  
Oral Administration ◽  
Early Exposure ◽  
System A ◽  
The Impact ◽  
Low Solubility ◽  
Low Solubility Drugs

scholarly journals BCS Class IV Oral Drugs and Absorption Windows: Regional-Dependent Intestinal Permeability of Furosemide

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1175
Author(s):  
Milica Markovic ◽  
Moran Zur ◽  
Inna Ragatsky ◽  
Sandra Cvijić ◽  
Arik Dahan
Keyword(s):  
Intestinal Permeability ◽  
In Silico ◽  
Oral Absorption ◽  
Critical Role ◽  
Oral Drugs ◽  
Absorption Window ◽  
Low Solubility ◽  
Class Iv

Biopharmaceutical classification system (BCS) class IV drugs (low-solubility low-permeability) are generally poor drug candidates, yet, ~5% of oral drugs on the market belong to this class. While solubility is often predictable, intestinal permeability is rather complicated and highly dependent on many biochemical/physiological parameters. In this work, we investigated the solubility/permeability of BCS class IV drug, furosemide, considering the complexity of the entire small intestine (SI). Furosemide solubility, physicochemical properties, and intestinal permeability were thoroughly investigated in-vitro and in-vivo throughout the SI. In addition, advanced in-silico simulations (GastroPlus®) were used to elucidate furosemide regional-dependent absorption pattern. Metoprolol was used as the low/high permeability class boundary. Furosemide was found to be a low-solubility compound. Log D of furosemide at the three pH values 6.5, 7.0, and 7.5 (representing the conditions throughout the SI) showed a downward trend. Similarly, segmental-dependent in-vivo intestinal permeability was revealed; as the intestinal region becomes progressively distal, and the pH gradually increases, the permeability of furosemide significantly decreased. The opposite trend was evident for metoprolol. Theoretical physicochemical analysis based on ionization, pKa, and partitioning predicted the same trend and confirmed the experimental results. Computational simulations clearly showed the effect of furosemide’s regional-dependent permeability on its absorption, as well as the critical role of the drug’s absorption window on the overall bioavailability. The data reveals the absorption window of furosemide in the proximal SI, allowing adequate absorption and consequent effect, despite its class IV characteristics. Nevertheless, this absorption window so early on in the SI rules out the suitability of controlled-release furosemide formulations, as confirmed by the in-silico results. The potential link between segmental-dependent intestinal permeability and adequate oral absorption of BCS Class IV drugs may aid to develop challenging drugs as successful oral products.

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