Introduction

Microneedle patches are modern systems for the transdermal delivery of active substances. One type of such systems comprises dissolvable patches based on natural polymers. A critical step in the preparation of these patches is to thoroughly fill the mold so as to obtain sharp tips of microneedles and remove all air bubbles. The aim of the study was to optimize the preparation process of dissolvable microneedle patches based on sodium hyaluronate.

Methods

For this purpose, 10 % w/w aqueous solutions of sodium hyaluronate were prepared using five different methods: (i) sonication, (ii) shaking, (iii) mechanical mixing, (iv) mechanical mixing combined with sonication, and (v) mechanical mixing combined with shaking. The resulting solutions were poured into silicone molds. In order to optimize the accurate filling of the mold and eliminate residual air bubbles, the molds with the solution were subjected to one of the following conditions: (i) no additional treatment, (ii) sonication, (iii) shaking, or (iv) three cycles of freezing and thawing.

Results

Preparation of the polymer solution using only sonication or a shaking was very time-consuming. Mechanical mixing alone or combined with shaking caused the solution to become aerated. However, mechanical mixing combined with sonication allowed the sodium hyaluronate to dissolve quickly and without aeration of the solution. The mold filled only by pouring the solution, or with using only ultrasounds or a shaker resulted in incomplete filling and the needles were not formed. On the contrary, three cycles of freezing and thawing allowed the mold to be completely filled and sharp needles were obtained.

Conclusions

Mechanical mixing combined with sonication was the most effective method for preparing a homogeneous, nonaerated polymer solution. The most efficient mold filling and sharp microneedle formation was achieved by applying three cycles of freezing and thawing to the filled molds.