A Novel, Optimized Method to Accelerate the Preparation of Injectable Poly-L-Lactic Acid by Sonication

August 2018 | Volume 17 | Issue 8 | Original Article | 894 | Copyright © August 2018


Chien-Nien Li MD,a,b Chao-Chin Wang MD,c Cheng-Chieh Huang MD,d Hsiao-Han Wang MD,e Nia-Jen Hsu MDf

aKuanshi Clinic, Taipei, Taiwan bDepartment of Dermatology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan cTainan Vigor Clinic, Tainan City, Taiwan dBeauté J’adore clinic, Taipei, Taiwan eDepartment of Dermatology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan fHsu Nai-Jen Clinic, Tainan City, Taiwan

Abstract
Current consensus for preparing injectable poly-L-lactic acid (PLLA) suggests adequate hydration (less than equal to 2-24 hours of reconstitution) of the lyophilized particles before injection, but the volume of reconstitution and the duration of hydration time varies. This study established a method to evaluate the distribution of PLLA particles after hydration and found that longer hydration time increased the effective portion (particles less than 60 μm) of PLLA products. Further investigation of the feasibility of reconstitution with sonication revealed that 2-hour hydration of PLLA powders with additional 5-minute-sonication could yield a comparable particle distribution with 48-hour-hydration of PLLA. Moreover, adding lidocaine into the diluent did not alter the distribution of PLLA particles. We proposed a new, feasible and efficient method of preparing PLLA injectable products: 2-hour hydration of the powders, sonication of the bottle or vial containing PLLA products for at least 5 minutes, and finalization with 1-2 mL of lidocaine immediately before injection. J Drugs Dermatol. 2018;17(8):894-898.

INTRODUCTION

Poly-L-lactic acid (PLLA; Sculptra®, Galderma, Fort Worth, TX) injection is an effective treatment option for correction of bony and soft tissue facial deficiencies.1 PLLA, as synthetic polymer derivative from the alpha-hydroxy family, stimulates fibroblastic response, which leads to neo-collagenesis and volume restoration.2 PLLA is available in vials as lyophilized milled powder, which requires reconstitution with sterile water and homogenous suspension of the particles before injecting into the skin.3Adverse reactions associated with PLLA include subcutaneous papule/nodule formation.5 These undesired subcutaneous papules, may result from insufficient reconstitution, variations in filling volumes, uneven product distribution in the suspension, imprecise or superficial injection technique, allergic or inflammatory host response or lack of posttreatment massage.5-7 Several methods have been described to minimize the occurrence of PLLA related adverse events.6,8 Recent consensus also specifically recommended increasing the volume of sterile water for hydration to 7-8 mL and lengthening the time of reconstitution to 24 to 48 hours or longer before injection.9,10 Finally, to provide local anesthesia, 1-2 mL of lidocaine (with or without epinephrine) can be added into the PLLA product immediately prior to injection.8,9 However, there were no existing studies regarding the changes of different sizes of PLLA particles during the time of reconstitution. Whether the addition of lidocaine affected the property of PLLA products has not been studied.Also, there was no controlled studies investigating the use of special mixing devices to assist the process of reconstitution. Common commercial ultrasonic cleaner has been used to shorten the time for decalcification procedures of skeletal tissues for pathology.11 The use of ultrasonic cleaner to facilitate the hydration and suspension of PLLA particles have not been documented in the literature.Our first aim was to investigate the property and size changes of PLLA particles during the whole process of reconstitution from 0 to 48 hours. We also investigated whether ultrasonic cleaner-assisted reconstitution could more rapidly achieve comparable results (proportion of effective particle sizes) as the standard protocol of 24-48 hours reconstitution time. Additionally, this study evaluated whether the infusion of lidocaine to the sonication-reconstituted PLLA would impact the particle stability of the solution.
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