Hot Melt Extrusion as a Formulation Method of Terpolymer Rods with Aripiprazole: A Preliminary Study

Abstract

Aripiprazole (ARP) is an atypical neuroleptic used in the therapy of mental diseases such as schizophrenia. The lack of optimal adherence to an oral therapy regime creates the basis for designing ARP long-acting injections. This study aimed to use 105 °C hot melt extrusion (HME) as a formulation method for rods based on poly(d,l-lactide-co-glycolide-co-trimethylene carbonate) with a molecular weight (Mn) of 21 kDa (Td,l 21), poly(l-lactide-co-glycolide-co-trimethylene carbonate) with a Mn of 59 kDa (Tl 59), and with a Mn of 77 kDa (Tl 77). The following methods were involved in the research: NMR, DSC, XRD, HSM, FTIR, GPC, SEM, and mechanical tests. HME at 105 °C (i) ensured flow behavior for terpolymers, (ii) did not influence the terpolymers’ composition and (iii) the polymorph changes of ARP, and (iv) resulted in the changes in terpolymers’ Mn. For the rods with ARP based on Td,l 21 (Td,l 21 rod-ARP) and Tl 59 (Tl 59 rod-ARP), plasticization was noted. No drug–terpolymer interactions were revealed. No pores were observed on the surface. Due to its high flexibility and rubber character, Td,l 21 rod-ARP may be proposed for intramuscular administration, whereas Tl 59 rod-ARP, due to its higher strength and moderate stiffness, is proposed for subcutaneous administration.

Keywords

• aripiprazole
• drug delivery system
• hot melt extrusion
• implant
• polymer
• differential scanning calorimetry