The acceptability of pediatric pharmaceutical products to patients and their caregivers can have a profound impact on the resulting therapeutic outcome. However, existing methodology and approaches used for acceptability assessments for pediatric products is fragmented, making robust and consistent product evaluations difficult. A pediatric formulation development workshop took place in Washington, DC in June 2016 through the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI). A session at the workshop was dedicated to acceptability assessments and focused on two major elements that affect the overall acceptability of oral medicines, namely swallowability and palatability. The session started with presentations to provide an overview of literature, background and current state on swallowability and palatability assessments. Five parallel breakout discussions followed the presentations on each element, focusing on three overarching themes, risk-based approaches, methodology and product factors. This article reports the key outcomes of the workshop related to swallowability and palatability assessments.
Encapsulation of drugs in mesoporous silica using co-spray drying process has been recently explored as potential industrial method. However, the impact of spray drying on manufacturability, physiochemical stability and bioavailability in relation to conventional drug load processes are yet to be fully investigated. Using a 2(3) factorial design, this study aims to investigate the effect of drug-loading process (co-spray drying and solvent impregnation), mesoporous silica pore size (SBA-15, 6.5 nm and MCM-41, 2.5 nm) and percentage drug load (30% w/w and 50% w/w) on material properties, crystallinity, physicochemical stability, release profiles and bioavailability of fenofibrate (FEN) loaded into mesoporous silica. From the scanning electronic microscopy (SEM) images, powder X-ray diffraction and Differential scanning calorimetry measurements, it is indicated that the co-spray drying process was able to load up to 50% (w/w) FEN in amorphous form onto the mesoporous silica as compared to the 30% (w/w) for solvent impregnation. The in vitro dissolution rate of the co-spray dried formulations was also significantly (p = 0.044) better than solvent impregnated formulations at the same drug loading. Six-month accelerated stability test at 40 °C/75 RH in open dish indicated excellent physical and chemical stability of formulations prepared by both methods. The amorphous state of FEN and the enhanced dissolution profiles were well preserved, and very low levels of degradation were detected after storage. The dog data for the three selected co-spray-dried formulations revealed multiple fold increment in FEN bioavailability compared to the reference crystalline FEN. These results validate the viability of co-spray-dried mesoporous silica formulations with high amorphous drug load as potential drug delivery systems for poorly water soluble drugs.
: Norvir® (ritonavir) is a Biopharmaceutical Classification System Class IV compound with poor solubility in water (~5 µg/mL) and limited oral bioavailability. Early stage development efforts were focused on an oral solution (OS) which provided reasonable bioavailability but exhibited taste-masking challenges and required the use of solvents with potential pediatric toxicity. Norvir® oral powder, 100 mg (NOP) was developed to replace OS. The objective of this study is to provide an overview of the development of NOP and palatability assessment strategy. Palatability of NOP was assessed using the flavor profile method: (1) As an aqueous suspension dose/response and (2) evaluation with foods. The dose/response sensory analysis indicated that NOP has strong intensity bitterness and burnt aromatics (3 on the 0–3 flavor profile scale) at the clinical dose (100 mg/10 mL) and the recognition threshold was determined to be 0.3 mg/10 mL. To improve palatability, 100 mg/10 mL NOP aqueous suspension was evaluated with foods. Consuming foods high in fat and/or sugar content after NOP administration successfully reduced bitterness to a 1.5 intensity. In summary, NOP provides dose flexibility, enhanced stability, eliminated solvents, and maintains consistent bioavailability, with reduced bitterness and improved palatability via administration with common food products.
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