Enhancement of carvedilol solubility by solid dispersion technique using cyclodextrins, water soluble polymers and hydroxyl acid

• We compared the effect of tartaric acid and ionization process on carvedilol.
• I3 formulation shows the prime effect on drug solubility and dissolution rate.
• It shows 0.861 mg/mL drug solubility (0.0301 mg/mL for pure drug) in pH 7.4.
• 94% of drug released within 30 min (15% for pure drug) in pH 7.4.
• From the overall reports we concluded I3 was appropriate one.

Aim of the present work is to enhance aqueous solubility of carvedilol (CV) by solid dispersion technique using wide variety of carriers such as: β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD), tartaric acid (TA), polyvinyl pyrrolidone K-30 (PVP K-30) and poloxamer-407 (PLX-407). Various products of ‘CV-solid dispersion’ had been studied extensively in various pH conditions to check enhancement of solubility and dissolution characteristics of carvedilol. Any physical change upon interaction between CV and carriers was confirmed by instrumental analysis: XRD, DSC, FTIR and SEM. Negative change of Gibb's free energy and complexation constants (Kc, 75–240 M−1, for cyclodextrins and 1111–20,365 M−1, for PVP K-30 and PLX-407) were the evidence of stable nature of the binding between CV and carriers. ‘Solubility enhancement factor’ of ionized-CV was found high enough (340 times) with HPβCD in presence of TA. TA increases the binding efficiency of cyclodextrin and changing the pH of microenvironment in dissolution medium. In addition, ionization process was used to increase the apparent intrinsic solubility of drug. In vitro, dissolution time of CV was remarkably reduced in the solid dispersion system compared to that of pure drug. This may be attributed to increased wettability, dispersing ability and transformation of crystalline state of drug to amorphous one.

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