Hs. Lin et al., 2-hydroxypropyl-beta-cyclodextrin increases aqueous solubility and photostability of all-trans-retinoic acid, J CLIN PH T, 25(4), 2000, pp. 265-269
Background: All-trans-retinoic acid (ATRA, vitamin A acid or tretinoin) is
effective in the treatment of acute promyelocytic leukaemia (APL). Unfortun
ately, the oral absorption of ATRA is highly variable. Its poor aqueous sol
ubility also makes it difficult to be formulated into parenteral formulatio
n To date, there is no parenteral formulation of ATRA available commerciall
y. O
bjective: To undertake the preformulation work necessary for developing suc
h a product.
Method: We investigated the solubility and stability profile of ATRA in var
ious formulations.
Results: The aqueous solubility of ATRA could be greatly increased by the i
nclusion of ATRA in 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD). Adjusti
ng the pH value further improved the water solubility of ATRA. The photosta
bility of HP-beta-D-based formulation of ATRA was evaluated and it was foun
d that inclusion ATRA into HP-beta-CD did improve the photostability of ATR
A.
Conclusion: These results showed that it is possible to develop a parentera
l formulation and/or an aqueous oral formulation of all-trans-retinoic acid
by using 2-hydroxypropyl-beta-cyclodextrin. However, the biopharmaceutical
properties of such a formulation would be necessary before its use.