With several marketed oral-administered drugs as nanosuspensions, the industry is weighing options to bring more molecules as nanosuspensions for long-acting injectable (LAI) applications.1 Examples include tizanidine (Zanaflex®), griseofulvin-PEG, fenofibrate (Tricor®), megestrol acetate (Megace® ES), dexmethylphenidate (Focalin® XR), aprepitant (Emend®), and sirolimus (Rapamune®).
LAIs and nanosuspensions have drawn much attention in today’s pharmaceutical industry because they can effectively address the delivery of challenging molecules across all modalities. Ascendia Pharmaceutical Solutions has become a CDMO Partner of Choice because we effectively address challenges that can stem from poor solubility, stability and increased viscosity of drugs with higher melting and logP.
Nanosuspensions are colloidal dispersions comprised of nano-sized drug particulates stabilized by the appropriate stabilizers.2 The nanosizing by homogenization or milling results in drugs with reduced particle size. It allows for higher per-volume loading, thereby, making them ideal for depot delivery by intramuscular and subcutaneous routes for injection and/or oral administration.3 Long- term stability of nanoparticles aided by utilization of excipients, polymers, solubilizer and/or surfactants, results from minimizing the electrostatic interactions, thus preventing the flocculation of drug in the crystalline state.
Excipients are commonly used alone or in combination of stabilizers for preventing the aggregation of nanosuspensions.4 Among excipients typically used are povidone, polysorbate 80, synthetic and natural lipids, cellulosic ingredients (MC, HPMC, EC, HEC, HPC, CMC), Soluplus®, Poloxamer 188, Poloxamer 407, sodium lauryl sulfate, polyvinyl alcohol, vitamin E TPGS, and polyethylene glycols.
Drug development teams prepare nanosuspensions via a wide range of methods. The figure to the left illustrates the top-down, wet milling and high-pressure homogenization and bottom-up precipitation and emulsions/microemulsions approaches for manufacturing of nanosuspensions.
Nanosuspensions, designed with nanosized crystals and stabilized by polymeric excipients and solubilizers and permeation enhancers, leverage added benefits for screening of broad range of new chemical entities (NCEs) across all modalities via injectable (IV, IM and SubQ), ocular, pulmonary, oral and topical route of administrations.
Ascendia Pharmaceutical Solutions remains at the innovation front of utilizing its proprietary enabling multiple platform nanotechnologies to screen, formulate and manufacture the NCEs for its clients. With Ascendia’s internal expertise and capabilities in top down and bottom up (solvent inversion) approaches coupled with its cGMP sterile and non-sterile capabilities and 60,000 square-foot state of-the-art facility and equipment, our team is ready to handle the small molecules and biologics across all modalities for oral, injectable, ocular, and inhalation delivery in nanosuspensions.
Contact us to discuss your next drug-development project and how we can help you overcome your challenges and bring it to market on schedule.
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