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. 2017 Mar;25(3):419-439.
doi: 10.1016/j.jsps.2016.09.013. Epub 2016 Sep 30.

Investigation of the in vitro performance difference of drug-Soluplus® and drug-PEG 6000 dispersions when prepared using spray drying or lyophilization

Mohammad A Altamimi  1 , Steven H Neau  2
Affiliations

Investigation of the in vitro performance difference of drug-Soluplus® and drug-PEG 6000 dispersions when prepared using spray drying or lyophilization

Mohammad A Altamimi et al. Saudi Pharm J. 2017 Mar.

Abstract

Purpose: To evaluate the physicochemical and in vitro characteristics of solid dispersions using BCS II model drugs with Soluplus® and one of its component homopolymers, PEG 6000.

Methods: Nifedipine (NIF) and sulfamethoxazole (SMX) of 99.3% and 99.5% purity, respectively, were selected as BCS II model drugs, such that an improved dissolution rate and concentration in the gastrointestinal tract should increase oral bioavailability. Soluplus® is an amorphous, tri-block, graft co-polymer with polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol (PCL:PVAc:PEG6000) in the ratio 57:30:13. PEG 6000 (BASF) is a waxy material with melting point of about 60 °C. Solid dispersions were prepared using lyophilization or spray drying techniques. Dissolution study, crystallinity content, and analysis for new chemical bond formation have been used to evaluate the dispersed materials.

Results: Although each polymer improved the drug dissolution rate, dissolution from Soluplus® was slower. Enhanced dissolution rates were observed with NIF solid dispersions, but the dissolution profiles were quite different due to the selected technique, polymer, and dissolution medium. For SMX, there was similarity across the dissolution profiles despite the medium, polymer, or applied technique. Each polymer was able to maintain an elevated drug concentration over the three hour duration of the dissolution profile, i.e., supersaturation was supported by the polymer. DSC thermograms revealed no melting endotherm, suggesting that the drug is amorphous or molecularly dispersed.

Conclusion: NIF and SMX solid dispersions were successfully prepared by spray drying and lyophilization using Soluplus® or PEG 6000. Each polymer enhanced the drug dissolution rate; NIF dissolution rate was improved to a greater extent. Dispersions with PEG 6000 had a faster dissolution rate due to its hydrophilic nature. DSC analysis showed that no crystalline material exists in the dispersions.

Keywords: Dissolution; Lyophilization; Nifedipine; PEG 6000; Solid dispersion; Soluplus®; Spray drying; Sulfamethoxazole.

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Figures

Figure 1
Figure 1
Chemical structures of a. nifedipine, b. sulfamethoxazole, c. polyethylene glycol, and d. Soluplus®.
Figure 2
Figure 2
DSC thermograms for (top to bottom) sulfamethoxazole, PEG 6000, Soluplus®, and nifedipine.
Figure 3a
Figure 3a
DSC thermograms of sulfamethoxazole:Soluplus® spray dried mixtures at a mass ratio of 1:1, 1:5, and 1:9.
Figure 3b
Figure 3b
DSC thermograms of sulfamethoxazole:PEG 6000 spray dried mixtures at mass ratios of 1:5 and 1:9.
Figure 4a
Figure 4a
DSC thermograms of nifedipine:Soluplus® spray dried mixtures at mass ratios of 1:1, 1:5, and 1:9.
Figure 4b
Figure 4b
DSC thermograms for nifedipine:PEG 6000 spray dried mixtures at mass ratios of 1:5, and 1:9.
Figure 5a
Figure 5a
DSC thermograms for sulfamethoxazole:Soluplus® lyophilized mixtures at mass ratios of 1:1, 1:5, and 1:9.
Figure 5b
Figure 5b
DSC thermograms for the sulfamethoxazole:PEG 6000 lyophilized mixtures at mass ratios of 1:1, 1:5, and 1:9.
Figure 6a
Figure 6a
DSC thermograms for the nifedipine:Soluplus® lyophilized mixtures at mass ratios of 1:1, 1:5, and 1:9.
Figure 6b
Figure 6b
DSC thermograms for nifedipine:PEG 6000 lyophilized mixtures at mass ratios of 1:1, 1:5, and 1:9.
Figure 7a
Figure 7a
DSC thermograms for SMX mixtures with Soluplus® and with PEG 6000 at a mass ratio of 1:9 stored for six months at 0% RH and 25 °C.
Figure 7b
Figure 7b
DSC thermograms for NIF mixtures with Soluplus® and with PEG 6000 at a mass ratio of 1:9 stored for six months at 0% RH and 25 °C.
Figure 7c
Figure 7c
DSC thermograms for SMX mixtures with Soluplus® and with PEG 6000 at a mass ratio of 1:9 stored for six months at 0% R.H. and 50 °C.
Figure 7d
Figure 7d
DSC thermograms for NIF mixtures with Soluplus® and with PEG 6000 at a mass ratio of 1:9 stored for six months at 0% RH and 50 °C.
Figure 8a
Figure 8a
FTIR analysis for the used materials.
Figure 8b
Figure 8b
FTIR analysis for SMX-polymer mixtures (S denotes spray dried, and L denotes lyophilized).
Figure 8c
Figure 8c
FTIR analysis for NIF-polymer mixtures (S denotes spray dried, and L denotes lyophilized).
Figure 9a
Figure 9a
Sulfamethoxazole and spray dried SMX with Soluplus® or PEG 6000 in SIF (n = 3). SMX alone in deionized water was added for comparison. Error bars represent standard deviation.
Figure 9b
Figure 9b
Sulfamethoxazole and spray dried SMX with Soluplus® or PEG 6000 in SGF (n = 3). Error bars represent standard deviation.
Figure 9c
Figure 9c
Sulfamethoxazole and lyophilized SMX with Soluplus® or PEG 6000 in SIF (n = 3). Error bars represent standard deviation.
Figure 9d
Figure 9d
Sulfamethoxazole and lyophilized SMX with Soluplus® or PEG 6000 in SGF (n = 3). Error bars represent standard deviation.
Figure 10a
Figure 10a
Nifedipine and spray dried NIF with Soluplus® or PEG 6000 in SIF (n = 3). NIF alone in deionized water was added for comparison. Error bars represent standard deviation.
Figure 10b
Figure 10b
Nifedipine and spray dried NIF with Soluplus® or PEG 6000 in SGF (n = 3). Error bars represent standard deviation.
Figure 10c
Figure 10c
Nifedipine and lyophilized NIF with Soluplus® or PEG 6000 in SIF (n = 3). Error bars represent standard deviation.
Figure 10d
Figure 10d
Nifedipine and lyophilized NIF with Soluplus® or PEG 6000 in SGF (n = 3). Error bars represent standard deviation.
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