Abstract
3D printing is a rapidly growing area of interest within pharmaceutical science thanks to its versatility in creating different dose form geometries and drug doses to enable the personalisation of medicines. Research in this area has been dominated by polymer-based materials; however, for poorly water-soluble lipophilic drugs, lipid formulations present advantages in improving bioavailability. This study progresses the area of 3D-printed solid lipid formulations by providing a 3D-printed dissolvable polymer scaffold to compartmentalise solid lipid formulations within a single dosage form. This allows the versatility of different drugs in different lipid formulations, loaded into different compartments to generate wide versatility in drug release, and specific control over release geometry to tune release rates. Application to a range of drug molecules was demonstrated by incorporating the model lipophilic drugs; halofantrine, lumefantrine and clofazimine into the multicompartmental scaffolded tablets. Fenofibrate was used as the model drug in the single compartment scaffolded tablets for comparison with previous studies. The formulation-laden scaffolds were characterised using X-ray CT and dispersion of the formulation was studied using nephelometry, while release of a range of poorly water-soluble drugs into different gastrointestinal media was studied using HPLC. The studies show that dispersion and drug release are predictably dependent on the exposed surface area-to-volume ratio (SA:V) and independent of the drug. At the extremes of SA:V studied here, within 20 min of dissolution time, formulations with an SA:V of 0.8 had dispersed to between 90 and 110%, and completely released the drug, where as an SA:V of 0 yielded 0% dispersion and drug release. Therefore, this study presents opportunities to develop new dose forms with advantages in a polypharmacy context.
Highlights
Mass manufacturing of oral formulations fails to produce drug forms that adequately address the complexity of an individual’s disease state, age and genetic factors [1,2,3].This “one-size-fits-all” approach has led to dose-related adverse drug reactions (ADRs), for older patients using polypharmacy [4,5,6]
The X-ray diffraction patterns in the Supporting Information (Figure S4) illustrate the crystalline nature of the lipids in the solid SMEDDS formulation, as the same peaks are apparent in the diffractograms for both the drug-free and drug-loaded SMEDDS
There were very minor diffraction peaks apparent for the SMEDDS where drug has been previously dissolved upon heating (‘Mixed’) at the positions of the major peaks in the corresponding reference crystalline drug
Summary
Mass manufacturing of oral formulations fails to produce drug forms that adequately address the complexity of an individual’s disease state, age and genetic factors [1,2,3]. This “one-size-fits-all” approach has led to dose-related adverse drug reactions (ADRs), for older patients using polypharmacy [4,5,6]. It is a technique that has been largely avoided in the 3DP of pharmaceutics due to the thermolabile nature of most drugs at temperatures required for its extrusion. FDM has gained greater interest with the development of new polymers that may be coextruded, with a drug, at lower temperatures to avoid thermal degradation during the extrusion process [21,22]
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