Research Article: Impact of Food and Drink Administration Vehicles on Paediatric Formulation Performance: Part 1—Effects on Solubility of Poorly Soluble Drugs

Date Published: June 26, 2020

Publisher: Springer International Publishing

Author(s): J. Martir, T. Flanagan, J. Mann, N. Fotaki.

http://doi.org/10.1208/s12249-020-01722-z

Abstract

Food and drinks are commonly used to facilitate administration of
paediatric medicines to improve palatability and enhance patient compliance.
However, the impact of this practice on drug solubility and on oral drug
bioavailability is not usually studied. Based on recommended strategies for oral
administration of paediatric medicines with food and drink vehicles, the aims of
this study were (i) to measure the physicochemical properties of (soft) food and
drink vehicles, commonly mixed with paediatric medicines prior to administration,
and (ii) to assess the impact of the co-administered vehicles on the solubility of
two poorly soluble paediatric drugs. Montelukast (sodium) and mesalazine were
selected as the model compounds. Distinct differences were observed between the
physicochemical properties (i.e. pH, surface
tension, osmolality, viscosity and buffer capacity) and macronutrient composition
(i.e. fat, sugar and protein content) of the
different soft foods and drinks, not only among vehicle type but also within
vehicles of the same subtype. Solubility studies of the two model compounds in
selected drinks and soft foods resulted in considerably different drug solubility
values in each vehicle. The solubility of the drugs was significantly affected by
the vehicle physicochemical properties and macronutrient composition, with the
solubility of montelukast being driven by the pH, fat and protein content of the
vehicles and the solubility of mesalazine by vehicle osmolality, viscosity and sugar
content. This vehicle-dependent impact on drug solubility could compromise its
bioavailability, and ultimately affect the safety and/or efficacy of the drug and
should be taken into consideration during paediatric product development.

Partial Text

Paediatric formulation development has been marked by new regulations,
additional funding opportunities and research initiatives in both the USA and
Europe. Nevertheless, development of acceptable, age-appropriate dosage forms,
whilst maintaining safety and efficacy and ensuring compliance, remains a challenge
due to the unique requirements and limitations of this heterogeneous population
(1,2).

(Soft) foods and drinks are commonly used to facilitate medicine
administration to the paediatric population in order to improve palatability and
enhance compliance. In this study, 26 vehicles that are commonly mixed with oral
medications for paediatric administration were characterised in terms of their
physicochemical properties and macronutrient composition. Differences were observed
across the range of food and drinks, notably not only among vehicles, but also
within vehicles of the same subtype These differences are expected to affect drug
behaviour, such as its solubility and dissolution, especially in the case of a
poorly soluble drug. Solubility studies of two model compounds, performed in
selected drinks and soft foods resulted in considerably different solubility values
in each vehicle. The solubility of the drugs was significantly affected by the
vehicle physicochemical properties and characteristics, with the solubility of
montelukast driven by pH, fat and protein content and the solubility of mesalazine
by vehicle viscosity, osmolality and sugar content. This vehicle-dependent impact on
drug solubility could compromise drug bioavailability and should be taken into
consideration during paediatric product development.

 

Source:

http://doi.org/10.1208/s12249-020-01722-z

 

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