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2‐Hydroxypropyl‐β‐cyclodextrin increases aqueous solubility and photostability of all‐ trans ‐retinoic acid
Author(s) -
HaiShu Lin,
C S Chean,
Yee Yung Ng,
Sui Yung Chan,
Paul C. Ho
Publication year - 2000
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1046/j.1365-2710.2000.00285.x
Subject(s) - solubility , retinoic acid , chemistry , beta cyclodextrins , cyclodextrin , aqueous solution , tretinoin , chromatography , pharmacology , organic chemistry , biochemistry , medicine , gene
Background: All‐ trans ‐retinoic acid (ATRA, vitamin A acid or tretinoin) is effective in the treatment of acute promyelocytic leukaemia (APL). Unfortunately, the oral absorption of ATRA is highly variable. Its poor aqueous solubility also makes it difficult to be formulated into parenteral formulation. To date, there is no parenteral formulation of ATRA available commercially. Objective: To undertake the preformulation work necessary for developing such a product. Method: We investigated the solubility and stability profile of ATRA in various formulations. Results: The aqueous solubility of ATRA could be greatly increased by the inclusion of ATRA in 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD). Adjusting the pH value further improved the water solubility of ATRA. The photostability of HP‐β‐CD‐based formulation of ATRA was evaluated and it was found that inclusion ATRA into HP‐β‐CD did improve the photostability of ATRA. Conclusion: These results showed that it is possible to develop a parenteral formulation and/or an aqueous oral formulation of all‐ trans ‐retinoic acid by using 2‐hydroxypropyl‐β‐cyclodextrin. However, the biopharmaceutical properties of such a formulation would be necessary before its use.