A systematic approach to design and prepare solid dispersions of poorly water-soluble drug

Abstract

The objective of the present study was to define a systematic approach to design and prepare solid dispersions of poorly water-soluble drug. The systematic approach can be defined in four phases. In the first phase, glass forming ability is assessed, and in the second phase, probable excipients are screened. The screened excipients are evaluated (third phase) for glass transition temperatures (Tg) and miscibility studies according to Florey-Huggins interaction parameter. The predicted excipients are used to prepare the solid dispersion and evaluated for Tg and any interactions using Fourier transfer infrared studies (fourth phase), and the findings are correlated with phase three predictions. For this investigation, cilostazol (CIL) was selected as model drug, which was classified as a poor glass former. As per the physical chemical properties of CIL, ten excipients, both polymeric and non-polymeric, were selected and screened. Out of these, povidone, copovidone, hypromellose and Eudragit EPO were found theoretically miscible with CIL. After going through phase 2 to phase 4, only povidone, copovidone and hypromellose were confirmed as polymer of choice for preparing the solid dispersion of CIL with a prediction of better physical solid-state stability on the basis of good miscibility between drug and carrier.

Fig. 1

Structure of cilostazol

Fig. 2

Systematic approach to design and prepare solid dispersions

Fig. 3

DSC thermogram of cilostazol

Fig. 4

pXRD diffractogram of cilostazol

Fig. 5

FTIR spectra of cilostazol

Fig. 6

SEM of cilostazol ×500

Fig. 7

SEM of cilostazol ×150

Fig. 8

Heat capacity as a function of temperature for crystalline and amorphous cilostazol

Fig. 9

Configurational heat capacity of cilostazol

Fig. 10

Fictive temperature as a function of temperature

Fig. 11

Phase diagram of cilostazol/PVP

Fig. 12

Phase diagram of cilostazol/copovidone

Fig. 13

Phase diagram of cilostazol/HPMC

Fig. 14

Phase diagram of cilostazol/EPO

Fig. 15

Melting point depressions of cilostazol with PVP, copovidone and HPMC

Fig. 16

Flory–Huggins interaction parameter of cilostazol with PVP

Fig. 17

Flory–Huggins interaction parameter of cilostazol with copovidone

Fig. 18

Flory–Huggins interaction parameter of cilostazol with HPMC

Fig. 19

FTIR spectra of cilostazol/PVP. From top to bottom: SD (1:4), SD (1:1), SD (4:1), pure povidone and pure CIL

Fig. 20

FTIR spectra of cilostazol/copovidone. From top to bottom: SD (1:4), SD (1:1), SD (4:1), pure copovidone and pure CIL

Fig. 21

FTIR spectra of cilostazol/HPMC. From top to bottom: SD (1:4), SD (1:1), SD (4:1), pure hypromellose and pure CIL