Achieving patient centricity through multiparticulate technology

Patient centricity has become a major focus in recent years across the pharmaceutical industry.​

The advantages of this approach have become increasingly evident, as every stakeholder in the system stands to benefit. Pharmaceutical companies can find that launching a product with non-ideal dosage forms, such as those having an unpleasant taste, can be addressed with the support of patient feedback. As a result, a follow-on product can be developed by reformulating the commercial product to encourage patient adherence and to improve health outcomes.

During drug development, the formulation of products can be carried out with certain patient groups in mind, such as paediatric or geriatric populations. These patients may have different requirements in the dosage forms, or in the release mechanism of the active pharmaceutical ingredient (API). An example is when certain patients have dysphagia, and therefore require formulations that are easier to swallow. The use of multiparticulate technologies in the drug development process is one method to ensure the needs of the drug developer and the patient can be fulfilled.

The capabilities of multiparticulate technology

Multiparticulate formulations are made up of multiple, small drug-containing particles that together make up a single dose. The multiparticulates can be referred to as particles, pellets, mini tablets, microsphere, granules or beadlets. They are generally delivered through oral solid dosage forms by being formulated into encapsulated, tablet or sachet formats. The particles can also be coated to provide certain properties, such as taste masking or to protect the drugs from the environment of the stomach. This type of drug formulation is seeing a greater amount of interest across the industry due to its inherent flexibility in creating a certain drug-release profile, both in single or multiple drug combinations. The technology also allows the formulation to provide modified or controlled release, as well as possessing other beneficial characteristics, such as bioavailability enhancement.

The particular technology suitable for the creation of the multiparticulate drug formulation will depend upon the API characteristics and the target product profile for the drug in development. It is possible to use lipid multiparticulate (LMP), spray-layered multiparticulate (SLM), as well as extrusion/spheronization and mini-tablet technologies to prepare the dosage forms. LMPs are round, smooth matrix multiparticulates that are typically 50 to 300 µm in diameter.

At Lonza, LMPs are produced using a continuous spinning-disc process, called melt-spray-congeal, which was developed to promote drug and particle size uniformity, while enabling versatile release profiles. SLMs are layered spherical particles approximately 100 to 1500 µm that contain one or more active ingredients. As with LMPs, SLMs can achieve good drug loading and particle size uniformity and can be tuned to offer a variety of modified release profiles as well as achieving amorphous forms of the API for bioavailability enhancement. SLMs are produced through a bottom-spray fluidized-bed coater to apply one or more coatings to a coating substrate.

Each approach has its advantages and disadvantages, but the technologies offer certain consistent benefits over standard oral dosage formulations. Multiparticulate formulations lower the chances of undesirable events associated with tablets, such as dose dumping, wherein the drug is metabolised too quickly. The technology also offers a more predictable and consistent rate of gastric emptying (e.g. transit from the stomach to the small intestine), potentially reducing clinical variability in drug absorption.

Lastly, when choosing a specific formulation and manufacturing approach, it is important to have a line of sight to both clinical and commercial manufacturing capabilities. Lonza offers end-to-end development and manufacturing capabilities for multiparticulate technologies, including small scale early phase development, pilot scale and clinical GMP manufacturing, and full commercial manufacturing capabilities – an end-to-end offering – for LMP, coated LMP and SLM formats. 

Better for all patients

The benefits to this approach in drug development do not end here, and there are certain traits to this technology that make it ideal when tailoring potential drugs for specific patient groups. One crucial quality is the ability to effectively mask the taste of the drug. This is particularly the case with paediatric patients, where poor taste of formulation can lead to worsened outcomes in adherence to treatments. However, this also holds true for adults, when certain formulations require large doses that can result in a taste that makes it difficult for patients to continue taking the treatment. By coating the particles through LMP or SML technology, this challenge can be overcome.

Another way to offer greater patient centricity over traditional pill formulations is the possibility to create an amorphous drug form through small pellets that are easily dosed, for people who have difficulty swallowing medicine. A further option is with sprinkled dosing, where the treatment can be packaged in a sachet and be delivered with food. This approach to drug formulation is ideal for paediatric and geriatric populations, who tend to have greater difficulty with swallowing larger tablets and capsules.

On the drug-release side of multiparticulates, the possibility to create controlled- and modified-release formulations also offers significant advantages to patients. The ability to control the release of the medication can negate the plasma spikes that occur when highly soluble, immediate-release formulations are absorbed rapidly by the body. When this occurs, there is the possibility that patients could experience greater side-effects from the treatment, which could be avoided if the dosage form allowed for the slow release of the drug.

In the clinical setting, multiparticulate treatments allow for a greater degree of flexibility in the doses that can be provided to patients. In the early stages of clinical development, the prospect of being able to offer a range of dose strengths that are easily achievable through multiparticulate technology offers advantages over the alternative of multiple tablet formulations, for example, by reducing the timeline and complexity of developing multiple tablet formulations. As a result, the dose range-finding studies can be completed more efficiently. For the participants of the trial, receiving a dose strength tailored to them can also help avoid unpleasant side effects.

Choosing the right partner

It is always important when talking to clients to outline that multiparticulate technology is not a silver bullet, it offers many advantages for the drug development process but, like every formulation technology, it has limitations as well. An example is that some compounds may not have sufficient thermal stability to be compatible with LMP technology.

Additionally, achieving high drug loadings with an SLM approach may be challenging. Occasionally, the benefits of multiparticulate technologies may be outweighed by these and other considerations, making more traditional approaches such as granulation/encapsulation and tableting more attractive choices. Lonza continuously works with clients to evaluate the suitability of formulation and manufacturing recommendations through a risk-based approach – in doing so, aims to design the best possible solution for advancement of the drug.

This is why working with a partner that has built up years of expertise and experience in the area is a must for those looking to explore the use of multiparticulate technology. Having a knowledgeable, science-driven partner means that potential pitfalls can be avoided due to prior experience navigating such issues.

As one of the few specialists in LMPs and a leader in multiparticulates, Lonza provides an end-to-end service that encompasses all stages of development, from building an in-depth knowledge of the drug, to taking partners all the way from feasibility studies through to commercialisation, thereby delivering the most suitable formulation for patients.