The inhibiting role of hydroxypropylmethylcellulose acetate succinate on piperine crystallization to enhance its dissolution from its amorphous solid dispersion and permeability

Abstract

The purpose of this study was to demonstrate that inhibiting crystallization by HPMCAS played a key role in enhancing dissolution and absorption of piperine (Pip) from its amorphous solid dispersion (ASD). Nucleation induction time and supersaturation tests were used to evaluate the ability of the polymers to inhibit crystallization of Pip. The prepared solid dispersions were characterized by DSC and FTIR. The dissolution rate of Pip from its ASDs was assayed by a dissolution test. Pip permeability was investigated by single-pass intestinal perfusion studies. The order of the ability of polymers to inhibit Pip crystallization was HF > MF > LF > L100-55. The best inhibition effect of HF can be attributed to its hydrophobicity and steric hindrance. Pip is amorphous in polymer matrices when the ratio of Pip/HPMCAS is lower than 1 : 1 and Pip/L100-55 is lower than 3 : 1. IR spectra show that there are hydrogen bonds between the amide groups of Pip and the carboxyl groups of polymer. The order of the ability of polymers to enhance Pip dissolution is HF > MF > LF > L100-55, which coincided with the ability of polymers to inhibit Pip crystallization. Increased apparent permeability via HF-induced supersaturation and decreased apparent permeability via solubilization with L100-55 are demonstrated. Nucleation induction time and supersaturation tests may be used to screen appropriate polymers for preparing ASDs.

Fig. 1. Schematic diagram of supersaturated parameters.

Fig. 2. The equilibrium solubility of Pip in the presence or absence of polymers.

Fig. 3. Desaturated curves of Pip supersaturated solutions in the presence or absence of polymers.

Fig. 4. Optical microscopic images of Pip crystal in the presence and absence of polymers ((A) no polymer; (B) L100-55; (C) LF; (D) MF; (E) HF).

Fig. 5. The change of extinction with time of Pip supersaturated solutions in the presence or absence of polymers.

Fig. 6. The DSC curves of 1 : 9 and 1 : 3 Pip solid dispersions (A); the DSC curves of 1 : 1 Pip solid dispersions (B); the DSC curves of 3 : 1 solid dispersions (C).

Fig. 7. (A) is IR spectra of crystal Pip and amorphous Pip; (B), (C), (D) and (E) are IR spectra of Pip/L100-55, Pip/HF, Pip/LF, Pip/MF solid dispersions with different proportions respectively.

Fig. 8. Dissolution curves of Pip, the 1 : 9 Pip/L100-55 and Pip/HPMCAS solid dispersions in pH 6.8 PBS.

Fig. 9. P _eff of from saturated solution, a solution containing L100-55 and a supersaturated solution in the presence of HF was assayed by single-pass intestinal perfusion studies. *p < 0.05 versus Pip solution. Average ± SD; n = 4.