Effect of Molar Mass of Hydroxypropyl β-cyclodextrin on the Aqueous Solubility of Dimenhydrinate

Dimenhydrinate (DMH) is used for the prevention and treatment of nausea, vomiting, dizziness and vertigo associated with motion sickness in a dose of 50 mg 1. It’s made of two drugs in a form of salt, diphenhydramine and 8-chlorotheophylline which synergically decrease motion caused neural excitation 2. DMH is classified as a slightly soluble drug and it belongs to class II of BCS classification as a drug with low solubility and high permeability 3. Cyclodextrins (CDs) are cyclic oligosaccharides formed by α-1,4-linked glucose units with a hydrophilic outer surface and a lipophilic central cavity. Formation of inclusion complex by incorporating a drug in the central CD cavity provides improvement of physicochemical properties without molecular modifications. Solubility and dissolution rate of poorly water-soluble drugs can be increased 4. Aqueous solubility of natural CDs is limited due to their tendency to form H-bonded associations. However, due to multiple reactive hydroxyl groups, their functionality can be greatly increased by chemical modification 5. CDs’ substituted derivates can overcome poor solubility issues and enhance bioavailability. Hydroxypropylβ-CD (HP-β-CD) has good inclusion ability, high water solubility and it’s safe for intravenous and oral administration 6. Stability constant (Ks) and complexation efficacy (CE) are important for assessing the binding characteristics of the drug and CD. They can be determined by the phase solubility studies where the change of the drug solubility is corresponding to the concentration of CD 7. Linear (AL) type of the curve implies that one molecule of the drug forms inclusion complex with one molecule of the CD. Apparent stability constant K1:1 can be calculated from the following equation: