Effect of Particle Size on the Dissolution Characteristics of Chlorthalidone

Narurkar, Arvind; Sheen, Pai‐Chang; Hurwitz, Ernest L.; Augustine, Matthew A.

doi:10.3109/03639048709040175

Cited by 1 publication

(1 citation statement)

References 7 publications

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“…Improving the solubility and dissolution rate of an orally administered drug can induce a higher amount dissolved in the gastrointestinal tract, and therefore, a more significant amount of drug is available for absorption into the bloodstream [15,16]. Diverse strategies have been developed to increase the dissolution of CTD, including reduction of the particle size [17], formation of inclusion complexes with β-cyclodextrin [18], microencapsulation by spray-drying and melt granulation coating [19], and incorporation into a solid self-micro-emulsifying drug delivery system (S-SMEDDS) [20]. In addition, the generation of amorphous forms by spray-drying with and without polymers was explored [21,22].…”

Section: Introductionmentioning

confidence: 99%

Tailoring Chlorthalidone Aqueous Solubility by Cocrystallization: Stability and Dissolution Behavior of a Novel Chlorthalidone-Caffeine Cocrystal

et al. 2022

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A cocrystal of the antihypertensive drug chlorthalidone (CTD) with caffeine (CAF) was obtained (CTD-CAF) by the slurry method, for which a 2:1 stoichiometric ratio was found by powder and single-crystal X-ray diffraction analysis. Cocrystal CTD-CAF showed a supramolecular organization in which CAF molecules are embedded in channels of a 3D network of CTD molecules. The advantage of the cocrystal in comparison to CTD is reflected in a threefold solubility increase and in the dose/solubility ratios, which diminished from near-unit values for D0D to 0.29 for D0CC. Furthermore, dissolution experiments under non-sink conditions showed improved performance of CTD-CAF compared with pure CTD. Subsequent studies showed that CTD-CAF cocrystals transform to CTD form I where CTD precipitation inhibition could be achieved in the presence of pre-dissolved polymer HPMC 80–120 cPs, maintaining supersaturation drug concentrations for at least 180 min. Finally, dissolution experiments under sink conditions unveiled that the CTD-CAF cocrystal induced, in pH-independent manner, faster and more complete CTD dissolution when compared to commercial tablets of CTD. Due to the stability and dissolution behavior of the novel CTD-CAF cocrystal, it could be used to develop solid dosage forms using a lower CTD dose to obtain the same therapeutic response and fewer adverse effects.

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