Assessment of selective laser sintering (SLS) 3D printing as a manufacturing technique for pediatric dosage forms

Abstract

Heterogeneity of the pediatric population means that several different requirements must be met in order to provide the pediatric population with medication suited to their needs. Due to different rates of development in terms of pharmacokinetics as well as motor skills children require tailored dosage forms where the dose of the active pharmacological ingredient (API) can be modified to their needs and the size of the medication is acceptable in order to avoid choking on the medications. In order to make sure that the child obtains the intended dose it is crucial that the developed dosage forms are palatable, ensuring adherence to the treatment. Selective Laser Sintering (SLS) has been employed as an additive manufacturing method capable of utilizing several thermoplastic and pharmaceutical grade polymer powders while providing flexibility in the manufacturing process due to its variable parameters as well as the ability to manufacture complex structures. Key parameters associated with dosage form manufacturing have to do with the energy density applied to the formulation powder which allows particles to undergo a sintering process where they are fused together though bridge formation without fully fusing together in a melt. Concerning energy density, Laser scanning speed (LSS), heating temperature and scan spacing have been identified as parameters with the most significant effect on the composition of the matrix. Oro-dispersible tablets (ODTs) as well as mini tablets have been chosen as key dosage forms for younger segments of the pediatric population as they present no swallowing difficulties. Vinylpyrrolidone-vinyl acetate copolymer (KVA64) was shown to be an optimal polymer for formation of ODTs. With favorable thermal properties such as Tg of ~100C as well as optimal spherical morphology and a relatively low particle size, at high LSS KVA64 was shown to be able to establish highly porous matrices that allowed for incorporation of various taste masking excipients as well as shielding of thermosensitive API by lowering printing temperature via plasticization. In order to manufacture minitablets, the laser scanning speed had to be lowered significantly and more coarse polymers were incorporated, allowing for denser formulations with reduced porosity. Drug release profiles were also tailored though utilization of Ethyl cellulose (EC) and poly (vinyl alcohol)–poly(ethylene glycol) graft copolymer (KIR) which due to their different chemical properties as well as size and morphology allow for sustained and instant release of API respectively. Incorporation of dual APIs was also demonstrated via matrix manipulation possible due to SLS’s layer by layer manufacturing. Manipulation of release profiles has also been shown for standard tablet formulations (10 mm) where altering the shape and the polymeric material by giving it more surface area as well modifying its internal structure to be more porous as in the case of a 95% pure Paracetamol dosage form allows for tailored drug release profiles.