Pharmaceutics, Drug Delivery and Pharmaceutical Technology
Effect of Substrates on Naproxen-Polyvinylpyrrolidone Solid Dispersions Formed via the Drop Printing Technique

https://doi.org/10.1002/jps.23397Get rights and content

ABSTRACT

Solid dispersions have been used to improve the bioavailability of poorly water-soluble drugs. However, drug solid-state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the drop printing (DP) technique can provide precise dosages and predictable compositional uniformity of active pharmaceutical ingredients in two-/three-dimensional structures when integrated with edible substrates. With different preparation conditions, DP was conducted to fabricate naproxen (NAP)–polyvinylpyrrolidone solid dispersions with chitosan and hydroxypropyl methylcellulose films as the substrate. Scanning electron microscopy, X-ray diffraction, second harmonic generation microscopy, and atomic force microscopy analyses were performed to characterize the microstructure and spatial distribution of NAP in the solid dispersions. The results identified that composition, temperature, and substrate type all had an impact on morphology and crystallization of samples. The surface energy approach was combined with classical nucleation theory to evaluate the affinity between the nucleus of NAP and substrates. Finally, the collective results of the drug were correlated to the release profile of NAP within each sample.

Section snippets

INTRODUCTION

The rapid screening of potential therapeutic agents has led to the discovery of increasingly poorly water-soluble drugs. As a result, enhancing the bioavailability of those hydrophobic active pharmaceutical ingredients (APIs) has become an important issue in the pharmaceutical industry. Preparations based on solid dispersions composed of a hydrophobic drug and a hydrophilic polymeric matrix have been recognized as some of the most promising methods to improve the bioavailability of APIs having

Materials

Naproxen was purchased from Spectrum Chemical (Gardena, California). PVP (K-90) and HPMC (E50) were kind gifts from ISP Technologies Inc. (Wayne, New Jersey) and The Dow Chemical (Midland, Michigan), respectively. Chitosan with a degree of deacetylation of approximately 85% was purchased from Koyo Chemical Company Ltd. (Tokyo, Japan).The molecular structures of NAP, PVP, HPMC, and chitosan are shown in Figure 1. All other reagents and solvents were of analytical grade.

HPMC Film

Hydroxypropyl

Scanning Electron Microscopy

The surface morphology of solid dispersions on different substrates was characterized by SEM. Figure 3a shows the solidified drop of 30:70 NAP–PVP on HPMC, which was dried at 25°C. This sample was visually transparent, and in Figure 3a, there was no solid formed in the drop, suggesting that the NAP mixed well with PVP without phase separation and appeared amorphous. The two small circular bright spots inside the drop were bubbles that formed when the solvent evaporated. SEM images of other

DISCUSSION

From the collective measurements, it is observed that the temperature of solidification has a profound impact on the morphology of the resulting NAP crystalline domains. Comparing Figures 3c and 3d or 3e and 3f, the SEM images of NAP–PVP that solidified at 25°C and 40°C, the morphology of the solid dispersions were different, suggesting a difference in the extent of crystal formation. This is verified by calculating the apparent crystallinity from the XRD data of 70:30 NAP–PVP on chitosan. For

CONCLUSIONS

The DP technique was found to work well on fabricating complex NAP–PVP solid dispersion products with chitosan and HPMC films. NAP–PVP (30:70) products remained amorphous 1 week after fabricating, and had a higher dissolution efficiency compared with those with higher NAP content. The samples that solidified at 25°C had higher crystallinity, whereas those solidified at 40°C had a larger crystal size. HPMC film was better at maintaining NAP in an amorphous state than the chitosan film, and had

ACKNOWLEDGEMENTS

The authors would like to acknowledge the financial support from the National Science Foundation Engineering Research Center for Structured Organic Particulate Systems. S.J.T. and G.J.S. gratefully acknowledge additional support from NIH-R01GM103401.

The authors declare no personal financial interests.

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