The requirements of the regulators responsible for the safety, quality and efficacy of orally inhaled and nasal drug products (OINDPs) place a heavy burden on those companies involved in the development and manufacture of those products in terms of testing.

Fully automated test systems have been developed to address these problems, however they do tend to be expensive, complex to operate and resource intensive to develop, validate and maintain.

In this instance, semi-automated systems available at a fraction of the cost of their fully-automated counterparts can provide a viable solution.

Copley Scientific supplies a broad range of labour saving devices and semi-automated systems for both Delivered Dose Uniformity and Aerodynamic Particle Size testing.

For comprehensive product details, specifications and part numbers, please request a copy of our brochure “Quality Solutions for Inhaler Testing”.

The build-up of static electricity on plastic, non-conductive surfaces such as those found in inhaler actuators and/or spacers can present specific problems with inhalers, particularly dry powder devices.

Generally speaking, metal objects such as impactors, particularly those manufactured from stainless steel do not present a problem.

Indeed, most problems of this nature emanate from the movement of the analyst around the laboratory prior to handling static sensitive equipment.

Irrespective of the source, it is preferable to take action to reduce static to a minimum on the grounds that it is one less variable capable of affecting the results.

Copley Scientific offers a range of equipment to monitor and minimise electrostatic effects in inhaler devices during the testing process.

For comprehensive product details, specifications and part numbers, please request a copy of our brochure “Quality Solutions for Inhaler Testing”.

The Pharmacopoeias recommend stage mensuration at regular intervals to ensure that only impactors within specification are used for testing inhaler output.

Unfortunately, because of the instrumentation, skill and time required to conduct a test, it is not practical to use stage mensuration on, for example, a daily basis. Currently, therefore, there is no practical means of checking the system suitability of an impactor on a daily or individual test basis.

Nozzle dimensional performance can however be indirectly monitored by measuring the pressure drop (Delta-P) across each stage of the impactor at a particular flow rate by using a suitable “Delta-P” Apparatus linked to a Flow Resistance Monitor.

For comprehensive product details, specifications and part numbers, please request a copy of our brochure “Quality Solutions for Inhaler Testing”.

The seals on cascade impactors can deteriorate with repeated use and exposure to solvent. Leaks then occur which because the system operates under vacuum allows air into the system causing erroneous results due to incorrect flow rates and poor aerodynamic performance.

For this reason, all cascade impactors should be tested on a regular basis to check the integrity of the sealing system. The most common method is to use a Leak Test Kit to block the entry to the impactor inlet, generate a vacuum within the impactor using a vacuum source and then monitor any rise in pressure using a pressure meter located within the enclosed system.

This method is sensitive, accurate, straightforward and fast. It is ideal for verification checks during the life of the impactor or, indeed, as a fast system suitability test before an impactor is used.

For comprehensive product details, specifications and part numbers, please request a copy of our brochure “Quality Solutions for Inhaler Testing”.

All inhaler testing systems should be tested on a regular basis as to their suitability for use.

The Qualification Kit includes all of the tools required to perform your Inhaler Testing IQ/OQ Qualification procedures.

It includes a vacuum regulation test rig, digital and absolute pressure meters, stop watch, temperature/humidity meter and all the associated tubing and fittings to qualify your inhaler testing system in-house, supplied in a handy carrying case complete with the required calibration certificates.

For comprehensive product details, specifications and part numbers, please request a copy of our brochure “Quality Solutions for Inhaler Testing”.

According to USP Chapter <1058>, Analytical Instrument Qualification is “the collection of documented evidence that an instrument performs suitably for its intended purpose”.

Whilst mensuration or calibration is an important part of the qualification process, it does not in itself qualify the whole inhaler testing system for use.

The Installation Qualification/Operation Qualification Documentation (IQ/OQ) provided by Copley Scientific guides the user through this important process and confirms that the system is fully qualified for use.

For comprehensive product details, specifications and part numbers, please request a copy of our brochure “Quality Solutions for Inhaler Testing”.

If stage mensuration results in an Effective Diameter in excess of an upper limit, then the stage must be replaced. This is a sign that the nozzles have worn, either as a result of corrosion from the solvents used to dissolve the active drug or erosion from the constant rapid passage of particles through the nozzles concerned. In this case, there is no further option available as it is not practical to reapply metal to impactor nozzles.

The majority of failed stages however relate to cases where the Effective Diameter decreases below the lower limit for the stage. This is usually caused by a build-up of hardened particulates or, more likely, because the corrosion process products metal salts that occlude the nozzle.

In this instance, a combination of ultrasonic cleaning and “stage pinning” is often sufficient to remove deposits and restore performance.

Impactor Stage Pinning involves pushing stainless steel “go” pins with a diameter between the nominal diameter and the lower tolerance limit for the stage through each nozzle in order to clear accumulated debris.

For comprehensive product details, specifications and part numbers, please request a copy of our brochure “Quality Solutions for Inhaler Testing”.

Both European and US Pharmacopoeias lay down certain criteria which the cascade impaction system and test criteria selected for the inhaler must fulfil prior to and during use.

The performance and reproducibility of a cascade impactor are dependent on a number of factors, the most critical being the nozzle dimensions (and their spatial arrangement) on each stage together with the air flow rate passing through it.

Providing these critical dimensions are within the quoted specification, then the impactors concerned can be expected to give comparable results.

The process of measuring the nozzle diameters and other critical dimensions of cascade impactors is called stage mensuration.

Both Ph.Eur. and USP recommend stage mensuration of impactors prior to use and periodically thereafter.

For comprehensive product details, specifications and part numbers on our stage mensuration services, please request a copy of our brochure “Quality Solutions for Inhaler Testing”.

Hitherto, the scientific community has used the terms “validation” and “qualification” on an interchangeable basis thus creating a degree of ambiguity as to their use.

For this reason, USP have suggested that:

a) the term “qualification” be applied to instrumentation and
b) the term “validation” to processes and software

Hence the term “Analytical Instrument Qualification (AIQ)” is used for ensuring that an instrument is suitable for its intended application, and the term “Analytical Method Validation” is used for ensuring that the analytical and software procedures employed are suitable for their intended application.

The USP Chapter <1058> Analytical Instrument Qualification describes in detail a four phase approach to qualification based on design (DQ), installation (IQ), operational (OQ) and performance (PQ) qualification.

For comprehensive details, specifications and part numbers of products and services associated with Qualification , please request a copy of our brochure “Quality Solutions for Inhaler Testing”.