Immediate Use After Reconstitution of a Biostimulatory Poly-L-Lactic Acid Injectable Implant

December 2020 | Volume 19 | Issue 12 | Original Article | 1199 | Copyright © December 2020


Published online November 28, 2020

Kerstin Baumann PhDa, Johanna Alm BSca, Maria Norberg PhDb, Maria Ejehorn MSca

aGalderma Aesthetics, Development, Uppsala, Sweden
bGalderma Aesthetics, Medical Affairs, Uppsala, Sweden

Abstract
Background: Poly-L-lactic acid (PLLA) is a biodegradable, synthetic polymer that stimulates collagen production and can improve skin quality, volume, and thickness. The current reconstitution procedure for Sculptra, a PLLA-containing injectable device involves 2 hours standing time before use.
Objective: To evaluate and validate an immediate-use procedure for reconstituting a PLLA-containing injectable device.
Methods and Materials: Three batches of the product were shaken for 1 minute immediately after reconstitution with 8 mL of sterile water. Different physicochemical tests including viscosity, concentration of excipients (sodium carboxymethylcellulose and mannitol), pH, and particle size distribution were performed for standing times 0, 2, 24, and 72 hours after immediate shaking, and compared with the standard 2 hours standing time before shaking. The recovery and stability of optional addition of 1 mL of 2% lidocaine hydrochloride was also assessed.
Results: All physiochemical parameters evaluated were equivalent, regardless of reconstitution procedure, showing that shaking vigorously for 1 minute dissolves the excipients of the product properly without a required standing time and with no impact to the PLLA particles. There were no differences in lidocaine hydrochloride content of suspensions after 0 and 72 hours.
Conclusion: The PLLA-containing product can be used immediately after reconstitution including vigorous shaking, as shown from physicochemical analyses. Optional addition of lidocaine hydrochloride is feasible.

J Drugs Dermatol. 2020;19(12):1199-1203. doi:10.36849/JDD.2020.5228

INTRODUCTION

Poly-L-lactic acid (PLLA) is a biodegradable, synthetic polymer that stimulates the production of collagen in the skin,1 and can improve the quality, volume, and thickness of the skin.2,3 PLLA is commercially available in injectable form as Sculptra™ (SCULPTRA® Aesthetic in the US), which is approved for use to restore a smooth and natural skin appearance in immune-competent people with shallow-to-deep nasolabial fold contour deficiencies and other facial wrinkles suitable for treatment with a cross-hatch injection technique.4

Sculptra has been shown to provide gradual improvement in skin thickness and appearance over several months, as measured by wrinkle assessment score and visual inspection,1,5,6 and the results can last over 2 years.6,7

Sculptra comprises powdered PLLA microparticles, with the excipients sodium carboxymethylcellulose (NaCMC) and mannitol. NaCMC acts as a suspending agent to maintain an even distribution of the PLLA particles and provides the suspension with a consistency suitable for injection following reconstitution.8 Mannitol is a sugar alcohol that acts as a bulk agent, enhancing the solubility of the product during reconstitution.8 Sculptra is used in the form of a suspension, reconstituted by the addition of sterile water for injection (SWFI). Prior to its approval by the US Food and Drug Administration in 2004, different groups of investigators used different methods to prepare Sculptra for injection.9 Hydration of the product was believed to be important and standing times of 2 to 168 hours were used.9 Since then, however, a standardized protocol for product preparation has been developed and was used in the pivotal trial that resulted in Sculptra approval.6 These reconstitution directions, which are included in the current US product label, state that 5 mL of SWFI should be added to the powder and, after 2 hours of standing time, the vial should be gently agitated and is then ready for use.4,6 The standing time was thought necessary to hydrate the product and to leave a uniform suspension, and the upper layer of foam that forms upon reconstitution was suggested to disappear over time if shaking was avoided. However, it has been shown that the NaCMC and mannitol excipients will instantly hydrate and dissolve when dispersed in water and shaken vigorously (data on file), providing a uniform suspension without increasing the formation of foam. The PLLA particles are insoluble in water and are expected to be uniformly distributed in the suspension from the viscosity achieved from the NaCMC excipient.