Improving drug solubility for oral delivery using solid dispersions.

https://cmapspublic3.ihmc.us/rid=1266358861321_2027852911_13457/Wound%20Healing%20Dressings%20and%20Drug%20Delivery%20Systems.pdf

Wound healing dressings and drug delivery systems: a review.

Microemulsion-based media as novel drug delivery systems

Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs.

Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.

Strategies to Address Low Drug Solubility in Discovery and Development

An investigation into the mechanisms of self-emulsification using particle size analysis and low frequency dielectric spectroscopy

An investigation into the physico-chemical properties of self-emulsifying systems using low frequency dielectric spectroscopy, surface tension measurements and particle size analysis

Characterisation of the glass transition of HPMC using modulated temperature differential scanning calorimetry.

Characterisation of polyethylene glycols using differential scanning calorimetry

A series of dispersions containing theophylline in Gelucires 43/01, 54/02, 50/02, 50/13 and 55/18 was prepared and the physical structures studied using differential scanning calorimetry. The dissolution, erosion and swelling profiles of the drug dispersions were assessed.



Gelucire 43/01 and 54/02 systems were found to release the drug by a simple diffusion mechanism, with no evidence for erosion or swelling being noted. Gelucire 55/18, however, showed a more complex mechanism involving both diffusion and erosion. On increasing the drug load within the matrices, the predominance of the erosion mechanism increased. Drug release from Gelucire 50/13 matrices took place principally by erosion, although the process was dominated by swelling and subsequent disintegration of the matrix, rather than simple dissolution of the base as was found for Gelucire 55/18. Gelucire 50/02 matrices also exhibited swelling, although drug release occurred predominantly via diffusion.



The study, therefore, demonstrates that Gelucires may release incorporated drugs by a number of mechanisms depending on the chemical composition of the base.

D.Q.M. Craig

Papers

An investigation into the mechanisms of self-emulsification using particle size analysis and low frequency dielectric spectroscopy

An investigation into the physico-chemical properties of self-emulsifying systems using low frequency dielectric spectroscopy, surface tension measurements and particle size analysis

Characterisation of the glass transition of HPMC using modulated temperature differential scanning calorimetry.

Characterisation of polyethylene glycols using differential scanning calorimetry

An evaluation of the mechanisms of drug release from glyceride bases.