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Spray drying – various challenges, one solution?

13 December 2016  •  Author(s): Nikki Whitfield, Quotient Clinical

Spray drying is a proven, flexible and scalable process used within the pharmaceutical industry to address a wide range of formulation and drug delivery challenges. Its versatility has been proven through applications to both small chemical and biopharmaceutical drugs for product delivery via multiple routes of administration. The technique is used to address stability challenges associated with temperature-sensitive molecules such as proteins and peptides, as well as providing innovative solutions for particle size critical applications such as inhaled drug delivery. In addition, the technology is now a primary formulation strategy to address an increasingly prevalent challenge in the industry: the successful oral delivery of poorly soluble compounds.

Optimising formulation for poorly soluble compounds

The prevalence of low or variable bioavailability in early clinical evaluation is increasing. Over 70% of new chemical entities display low aqueous solubility (defined as the highest dose strength that is insoluble in 250mL aqueous media over the physiological pH range at 37°C). Delivery of a poorly soluble drug, when formulated as a simple drug in capsule, or drug in bottle formulation – without dispersion aids, solubility enhancers or precipitation inhibitors – will limit the dissolution and hence solubility of the drug in the gastrointestinal (GI) tract. Consequently, the sub-optimal dissolution profile or subsequent precipitation of the drug during the transit through the GI tract will result in poor or variable absorption and systemic bioavailability. This presents an associated risk of sub-optimal or variable clinical data, creating a challenge when evaluating the potential of a drug candidate.

As most drugs exist in crystalline form, the energy required to break down the crystalline lattice and enable solubilisation is high. A ‘spring and parachute’ analogy is often used to describe the desired formulation strategy for such compounds. Firstly, modification of the drug properties or incorporation of formulation aids can give rise to enhanced solubilisation of the drug, depicted as the ‘spring’, and then the use of further functional excipients to prevent and prolong the onset of drug precipitation provides the ‘parachute’ effect1 . Spray drying is increasingly being applied to achieve this ‘spring and parachute’ profile as it produces an amorphous form of the drug compound in a higher energy, glassy state, which then leads to a faster dissolution rate compared to its crystalline form. Co-spray drying the compound with an excipient can prolong the time the drug is in the amorphous form to ensure rapid dissolution (the ‘spring’), promoting a supersaturated state and allowing the drug to remain in solution for an extended period of time in the intestinal milieu (the ‘parachute’ effect). 

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