Dissolution Testing For Inhaled drugs - Pharmaceutical Technology

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Dissolution Testing For Inhaled drugs
Although there are no regulatory requirements or established pharmacopoeial techniques for the dissolution testing of inhaled drugs, such testing can potentially open up the opportunity to tailor formulation properties. The authors explain how a new technique using standard dissolution test equipment in combination with US Pharmacopeia methods for the dissolution testing of solid dosage forms can be used to differentiate the solubility of orally inhaled products.

Pharmaceutical Technology Europe
Volume 22, Issue 11

Assessing the need for dissolution testing for inhaled drugs

For solid oral dosage forms, such as tablets and capsules, dissolution testing is standardised and routine. The dissolution profile of a product guides formulation and development, and is a widelyused QC tool. Dissolution data may also be used to support claims of parity in a generic product and/or to demonstrate equivalence following a formulation change since it is sufficiently sensitive to identify outofspecification manufactured batches.

With orally inhaled products (OIPs), the efficiency of drug delivery is linked with the extent of deposition in the respiratory tract. A particle size of less than 5 m is usually regarded as optimal for penetration to the deep lung, so the focus is to develop device/formulation combinations that deliver a high proportion of the dose in this size range: a high fine particle dose (FPD).1

As with solid dosage forms, the therapeutic effect of an inhaled powder is realised via dissolution and subsequent absorption. Powders delivered to the lung are, of necessity, extremely fine, so there may be an assumption that dissolution rates are rapid enough to have little impact on the overall process of drug delivery. Within a recent USP Pharmacopeial Forum review,2 however, it was recognised that dissolution testing may expand our understanding of inhaled drug delivery and support the development of new OIPs. This view is reinforced by industrial interest in the topic, as exemplified by recent work presented by GlaxoSmithKline contrasting the dissolution profile of a longacting beta agonist with that of an inhaled corticosteroid.3 If inhalation technologies follow the same development trajectory as tablets, there is no reason why the modification of particle properties, such as size, shape or crystal habit, to control in vivo release rate should not become routine. Formulations based on liposome, micelle and microsphere technologies also provide for more closely tailored delivery profiles.4,5 The trend towards the pulmonary route for the delivery of systemic drugs strengthens the impetus for refining OIP performance in this way.

Understanding the requirements for OIP dissolution testing

From a practical viewpoint, in vitro dissolution testing for inhalable products should be able to distinguish between samples in a way that replicates trends found in vivo . This suggests that test conditions should reflect the pulmonary environment. Perfectly designed for absorption, the lungs are not ideal from the point of view of dissolution, with fluid levels in the region of 10 to 20 mL/100 m2 of surface. Such small amounts of liquid are likely to be stagnant, inhibiting dissolution. Also, the exact composition of the aqueous fluids and surfactants lining the respiratory tract is not accurately known,6 which complicates the selection of a test medium.

Equally importantly, testing must also consider the delivery characteristics of OIPs. Just a portion of the emitted dose, the FPD, enters the lung so dissolution testing of the whole dose is inappropriate. A better aim is to access the dissolution profile of only those particles that will deposit in the lung.


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