The dissolution solution: meaningful drug development
At the heart of pharmaceutical testing, is drug dissolution, a crucial stage in drug development. Dissolution testing is formulated to assess the drug release rate from a particular dosage form, evaluating the intrinsic ability of the drug to dissolve and absorb into the bloodstream.
In other words, the dissolution profile obtained from testing helps assess the effectiveness of a drug for in-vivo performance.
Although vital, dissolution testing doesn’t come without its challenges. In order to ensure sufficient drug development and quality control, it is crucial that this kind of pharmaceutical testing is completed in appropriate, accurate and optimal testing conditions.
The fundamentals of dissolution testing
Dissolution testing is critical for the overall analysis of drug performance, whether it be solid, semisolid or liquid dosage forms. This testing is an obligatory step included within various phases of drug development, to ensure product optimisation at the early stages of R&D, or to perform stability assessment, evaluating formulation changes over time.
Regardless of where dissolution testing is during a drug evaluation cycle, it is used to qualify the drugs optimum performance ability.
This pivotal, in-vitro assessment, is designed to simulate in-vivo conditions accurately. This is why several conditional factors must be evaluated to formulate an appropriate testing method, including apparatus type, media and agitation rate.
From an FDA perspective, dissolution methods must also meet rigorous safety and quality regulations in order for a drug to be qualified for its introduction to the public.
Given both its unnegotiable importance and the attention to detail that’s required for accurate testing, the process has become heavily reliant on purpose-built environments within a cGMP compliant facility. The testing process is now highly technique-dependent, with specialised skills and techniques required as a standardised procedure.
Dissolution testing conditions
To assess the dissolution profile of a drug and subsequently, it’s in-vivo performance, a discriminatory method must be formulated that’s sensitive to all variables that could affect the dissolution rate. Here, an evaluation of how the APIs (active pharmaceutical ingredients) release over time are assessed to monitor how they’re absorbed into the circulatory system.
Various pharmacopoeias offer a definitive procedural outline for dissolution testing. External factors, including the apparatus used, proposed processes, dissolution media, and appropriate evaluations, can all have an effect on the results. This also transcends to small factors including the paddle rotation speed and sink conditions.
Consequentially, it is vital that all variables are controlled and specified during the analytical method to ensure accuracy and reliability.
Dissolution apparatus
There are 4 types of dissolution apparatus defined in the United States Pharmacopeia (USP); basket type (1), paddle type (2), reciprocating cylinder (3) and flow-through cell (4). [AS1]
The apparatus used is dependent on the dosage form being tested, with the most common methods of dissolution testing being USP Apparatus 1 and 2 which is mainly used for oral, solid dosage forms.
Although most commonly used, it still holds some disadvantages, one example being its inability to easily imitate gastrointestinal transit. Using a reciprocating cylinder (Apparatus 3) provides a more accurate in vitro-in vivo correlation.
Given that the evaluation of each apparatus is a necessary step in defining the right testing method, outsourcing your testing to a pharmaceutical testing facility can ensure that the right apparatus is used during method development.
HMR’s headquarters host 15 expansive labs catered to various pharmaceutical tests. Our experienced team of scientists, with over 30 years’ experience, are comfortably familiar with each apparatus, ensuring dissolution with different mediums at different speeds and volumes. Allowing for flexible in-vitro vivo modelling and other drug requirements.
Dissolution Media
Expertise is important in selecting the appropriate dissolution media, which depends on various factors. These factors include the purpose of the test, the APIs solubility, and the type of dosage form, i.e. immediate-release or modified-release. Ideally, the dissolution media should also meet sink conditions.
Methodology development
With the pharmaceutical market competitiveness growing, and with the inherent race to the shelf, it’s imperative for dissolution testing to be performed with high efficiency. Failure can be both a costly and timely consequence, which inevitably slows down the drug development process. As a result, the need for optimal procedure and methodology should be of utmost importance. This can be ensured through:
Highly trained specialists
Good quality dissolution chemists are important, as a level of high observance and excellent time management skills are necessary. Full anticipation of expected variations, and having a thorough understanding of the method, its properties and rigidness mean that experienced, highly trained professionals are best equipped for dissolution testing.
Chemists must have confident ability to determine any source of error that may occur, accurately proving that failure was directly determined by the dosage form. Chemists must clarify and minimise any aspects that could affect the dissolution rate, including coning, tablet-sticking, or air bubbles. All of which must be examined to assess any correlation with the dissolution rate.
Both analyst error or a poorly validated method could lead to failure during dissolution testing, highlighting the importance of collaboration with highly trained specialists with direct product knowledge, experience of apparatus and all appropriate dissolution methods.
HMR are an end-to-end provider with a highly experienced team and a comprehensive service range. From raw material testing, to finish product assessment, HMR works alongside you to fulfil your analytical testing needs throughout each step of your drug manufacturing journey.
Optimal environment
The initial apparatus quality, maintenance, calibration and overall care are imperative for optimal performance in dissolution testing. The operational ability must be at 100% before testing, as this can affect the dissolution rate and performance results.
For example, vibration is a well-documented factor that can affect dissolution rates, and must be considered within the testing environment. Both system and environmental vibration can affect dissolution rate. With high vibration levels able to generate a false passing result, even heavy foot traffic or nearby equipment must be controlled.
To minimise system vibration, it’s vital that the dissolution apparatus remains calibrated and well-maintained. Consequently, a separate laboratory devoted to dissolution testing will better avoid equipment problems stemming from vibration and other related issues.
Utilizing a third-party testing provider is an ideal route to access a lab area dedicated to dissolution, ensuring testing avoids outside variables that affect results. HMR’s dissolution lab with state-of-the-art instrumentation includes a full range of dissolution apparatus, able to fulfil all dissolution testing requirements.
HMR are the dissolution solution
Given the vast complexity and systematic testing needed for drug development, harboring a more streamlined, efficient and flexible approach process is valuable to many on their journey towards batch release. Using an experienced testing provider that can qualify both method development and validation before assessing drug performance is highly advantageous in helping to achieve your goal.
Given the longevity of the drug development life cycle, fostering a long-term partnership with a provider that can fulfil all of your pharmaceutical testing requirements within highly flexible timescales can further generate a streamlined drug development process. Helping you to achieve your results at a faster rate.
The best way to ensure the crucial testing conditions needed for dissolution procedures is by utilising HMR. Get in touch to find out how we can assist you today.