Preparation and Evaluation of Solid Dispersions of A New Antitumor Compound Based on Early-Stage Preparation Discovery Concept

Abstract

Ensuring sufficient drug solubility is a crucial problem in pharmaceutical-related research. For water-insoluble drugs, various formulation approaches are employed to enhance the solubility and bioavailability of lead compounds. The goal of this study was to enhance the dissolution and absorption of a new antitumor lead compound, T-OA. Early-stage preparation discovery concept was employed in this study. Based on this concept, a solid dispersion system was chosen as the method of improving drug solubility and bioavailability. Solid dispersions of T-OA in polyvinylpyrrolidone (PVP) K30 were prepared by the solvent evaporation method. Dissolution testing determined that the ideal drug-to-PVP ratio was 1:5. X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry were employed to confirm the formation of solid dispersions. Scanning electron microscopy demonstrated that T-OA was converted into an amorphous form. Both in vitro dissolution testing and the in vivo studies demonstrated that the solubility and bioavailability of T-OA were significantly improved when formulated in a solid dispersion with PVP. The dissolution rate of the T-OA/PVP solid dispersion was greatly enhanced relative to the pure drug, and the relative bioavailability of T-OA solid dispersions was found to be 392.0%, which is 4-fold higher than the pure drug.

Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs

“…Solid dispersions of indomethacin in mannitol/urea were prepared by fusion and effervescence assisted fusion techniques; the effervescence assisted fusion technique enhances the solubility and dissolution better than the conventional method (15). Solid disp e r s i o n o f a n a n t i c a n c e r c o m p o u n d ( T-O A ) i n polyvinylpyrrolidone (PVP) K-30 prepared by the solvent evaporation method improves the solubility, dissolution, and bioavailability of the compound (16).…”

Amino Acid Derivatives of Ligustrazine-Oleanolic Acid as New Cytotoxic Agents

“…In the earlier studies in this field, several ligustrazine derivatives had been designed, synthesized and biologically evaluated [3,4,5,6]. Thereafter, a novel anticancer lead compound 3 β- hydroxyolea-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (TOA, C 38 H 58 O 3 N 2 , Figure 1) was screened [6,7,8,9,10,11]. TOA was synthesized by conjugating the effective antitumor ingredients ligustrazine (TMP) and oleanolic acid (OA).…”

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“…The volume was made up to the mark with methanol. The solution was suitably diluted with methanol and spectrophotometrically assayed for DC at 284 nm using the following formula: [17,18] Percent DC = Concentration of drug releasedin medium Labeled claim ×1 100…”