Novel patchouli alcohol ternary solid dispersion pellets prepared by poloxamers

Abstract

The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of poorly water soluble bioactive constituent patchouli alcohol (PA) that can be used for the preparation of immediate release pellets formulation. Two commercially available grades poloxamer 188 (P 188) and poloxamer 407 (P 407) were selected, and solid dispersions (SDs) containing different weight ratio of PA and poloxamers, and the combination of P 188 and P 407 as dispersing carriers of ternary solid dispersions (tSDs) were prepared by a low temperature melting method and solidified rapidly by dropping into the 10-15 °C condensing agent atoleine. Both PA/P 188 and PA/P 407 binary solid dispersions (bSDs) could remarkably promote the dissolution rate of PA, increasing approximately 16 times in bSDs with poloxamers in comparison with pure PA within 180 min. P188 contributed to a faster dissolution rate than P 407, however, P 407 had a better solubility. It is interesting to note that the incorporation of P 188 in PA/P 407 bSD pellets could strongly enhance the dissolution rate of PA. DSC and FTIR were used to explore the characteristics of PA-SD pellets. The enhancement of dissolution from the SDs may be attributed partly to the reduction in particle size in PA crystalline due to the formation of eutectic system with poloxamers. Moreover, a simple, accurate in-vitro dissolution test method for volatility drug was established, and the process of PA-SD pellets preparation was simple, rapid, cost effective, uncomplicated and potentially scalable.

Keywords: Closed in-vitro dissolution test method; Eutectic mixtures; Patchouli alcohol; Poloxamers; Ternary solid dispersion pellets.

Figure 1

(A) Chemical structure of PA. (B) Chemical structure of Poloxamers P 188 (a=75-85, b=25-30) and P 407 (a=95-105, b=54-60).

Figure 2

The effect of open/closed systems on dissolution profiles of (a) open system, (b) closed system. Each point represents the mean ± SD (n = 3).

Figure 3

In - vitro release profiles of bSD pellets at different PA/poloxamers ratios. Each point represents the mean ± SD (n = 3).

Figure 4

The dissolution profiles of bSD pellets at different PA/P 407 ratios and tSD pellets at different PA/P 407/P 188 ratios. Each point represents the mean ± SD (n = 3).

Figure 5

In - vitro release profiles of tSD pellets at different PA/P 407/P 188 ratios. Each point represents the mean ± SD (n = 3).

Figure 6

DSC curves of PA, P 407, P 188, physical mixtures and SD pellets.

Figure 7

Binary phase diagram of PA/P 188 bSD pellets. The lines have no theoretical significance.

Figure 8

Binary phase diagram of PA/P 407 bSD pellets. The lines have no theoretical significance.

Figure 9

Ternary phase diagram of PA/P 407/P 188 tSD pellets.

Figure 10

FTIR spectra of PA, P 188, physical mixture and bSD pellets

Figure 11

FTIR spectra of PA, P 407, physical mixture and bSD pellets.

Figure 12

FTIR spectra of PA, poloxamers, physical mixture and tSD pellets