| Summary: | There is a significant need for research and development into paediatric medicines. The absence of suitable medicines or critical safety and efficacy information, poses significant risks to a particularly vulnerable patient population. The paediatric population is made up of a wide range of individuals of substantially varied physical size, weight and stage of physiological development. Some commonly used excipients may be unsuitable for use in children; and some dosage forms may be undesirable to the paediatric population. There is a need for a dosage form platform that is designed to meet the needs of the paediatric patient. The dosage form should offer dose flexibility, dose accuracy, afford acceptable taste of undesirable tasting drug substances and be suitable for administration to all paediatric sub groups. To ensure affordability and thus enhance access to medicines for children in developing countries or emerging markets, the dosage form should be simple to manufacture without the need for specialised equipment. Spray-drying was investigated to co-process a functional polymer, hypromellose, with a model drug substance, paracetamol, to enhance the functionality of the polymer and to taste mask the paracetamol. Though hypromellose was successfully spray-dried it was not possible to spray-dry hypromellose with paracetamol. The viscosity of aqueous solutions of hypromellose played a key role in determining the grade and concentration of hypromellose that could be successfully spray-dried. Temperature was used to reduce viscosity of hypromellose solutions but careful temperature control is required to avoid reaching the gelation temperature of the hypromellose. The effect of temperature on aqueous hydroxyl propylcellulose (HPC) solutions showed that heating causes a reduction in solubility of HPC in water which results in its precipitation and the formation of liquid crystals. Consequently, the aqueous HPC solutions appear ‘cloudy’ and their viscosity decreases. The temperature at which these changes occur is referred to as the ‘cloud-point’. The effect of temperature on aqueous HPC solutions containing drug is dependent on the properties of the drug. Paracetamol decreased the temperatures of dehydration and onset of precipitation and ranitidine hydrochloride increased the temperatures of dehydration and precipitation. This is probably associated with a salting in effect. HPC was used to form films which disintegrate in <30 seconds but are able to retard dissolution rate of paracetamol. HPC may be used to form films which meet the pharmacopoeial content uniformity criteria typically applied to oral dosage forms. HPC films have application for administering drugs to paediatric or geriatric patients by disintegrating in the mouth and so overcoming swallowing difficulties; potentially providing taste masking and aiding absorption across the oral cavity. HPC films offer significant benefits to the paediatric population. The manufacturing process is simple and transportation is easy as secondary packs are likely to be less bulky than currently used for tablets. The films may also be suitable for administering combinations of drugs in the same dosage form by layering or by combining the drugs at the HPC solution stage. For these reasons the HPC films may have particular application for diseases in the developing world and meet many requirements associated with WHO and other global regulatory guidelines.
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