Formulation of a Danazol Cocrystal with Controlled Supersaturation Plays an Essential Role in Improving Bioavailability

S.L. Childs, Praveen Kandi, Sreenivas R. Lingireddy
In: Molecular Pharmaceutics · 2013 · vol. 10(8) , pp. 3112–3127 · doi:10.1021/mp400176y · PMID:23822591 · W2055834732
article OA: bronze CC0 ⤵ 3 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-07 ⓘ

A danazol:vanillin cocrystal's bioavailability was improved over 10-fold by a supersaturating formulation containing vitamin E-TPGS and Klucel LF Pharm, compared to a neat suspension.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

Cocrystals have become an established and adopted approach for creating crystalline solids with improved physical properties, but incorporating cocrystals into enabling pre-clinical formulations suitable for animal dosing has received limited attention. The dominant approach to in vivo evaluation of cocrystals has focused on deliberately excluding additional formulation in favor of "neat" aqueous suspensions of cocrystals or loading neat cocrystal material into capsules. However, this study demonstrates that, in order to take advantage of the improved solubility of a 1:1 danazol:vanillin cocrystal, a suitable formulation was required. The neat aqueous suspension of the danazol:vanillin cocrystal had a modest in vivo improvement of 1.7 times higher area under the curve compared to the poorly soluble crystal form of danazol dosed under identical conditions, but the formulated aqueous suspension containing 1% vitamin E-TPGS (TPGS) and 2% Klucel LF Pharm hydroxypropylcellulose improved the bioavailability of the cocrystal by over 10 times compared to the poorly soluble danazol polymorph. In vitro powder dissolution data obtained under non-sink biorelevant conditions correlate with in vivo data in rats following 20 mg/kg doses of danazol. In the case of the danazol:vanillin cocrystal, using a combination of cocrystal, solubilizer, and precipitation inhibitor in a designed supersaturating drug delivery system resulted in a dramatic improvement in the bioavailability. When suspensions of neat cocrystal material fail to return the anticipated bioavailability increase, a supersaturating formulation may be able to create the conditions required for the increased cocrystal solubility to be translated into improved in vivo absorption at levels competitive with existing formulation approaches used to overcome solubility limited bioavailability.

My notes (saved in your browser only)

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (79)

Cited by (3)

Source provenance

openalex
last seen: 2026-05-10T11:21:38.221344+00:00
License: CC0 · commercial use OK