Classical Pharmaceuticals
Small Molecule Manufacturing Expertise

Strategies for Solid Formulation

The complexity of manufacturing solid formulation has become ever more challenging due to limitations around active pharmaceutical ingredient (API) stability, release kinetics and bioavailability. Also, manufacturers of solid dose drugs (especially generics) need to find ways to reduce manufacturing costs and optimize process efficiency. Our expertise can help you overcome some of these challenges.


1. Improving Solubility of APIs via Different Approaches


Improving Solubility of APIs via Different Approaches

Solubility enhancement is a key challenge in pharmaceutical formulation development, as an increasing number of APIs in the development pipeline are reported to be poorly water-soluble. For this reason, there is an immediate need for manufacturers to consider solubility enhancement approaches to ensure these formulations’ efficacy and their successful commercialization.

Solution

Different approaches are available to enhance the solubility of poorly water-soluble APIs. There is no one-size-fits all solution available and, depending on the API and intended use, different solutions might be suitable. Learn more about the use of drug carriers, spray-drying, and hot-melt extrusion as methods to improve the solubility of APIs for classical pharma applications.

2. Dosing Accuracy Considerations in Dry Powder Inhalation


Dosing Accuracy Considerations in Dry Powder Inhalation

Inhalation drug delivery methods are attractive, noninvasive routes when rapid onset of action, minimal side effects and excellent bioavailability are desired. Accurate dosing of the dry powder inhalation (DPI) formulation can be challenging due to the small amount of dosage and fine particle size required. A combination with solid excipient carriers is often necessary to improve drug stability, dose control and prevent particle cohesion. Currently, most powder blends for DPI formulations are based on lactose monohydrate as an excipient carrier. Challenges using a lactose-based excipient include possible interaction of the lactose (being a reducing sugar) with the API, and concerns for patient lactose intolerance or the use of an excipient of animal origin.

Solution

A new excipient based on mannitol may help to overcome some of these challenges, as it is physiologically and chemically inert with reducing sugar levels below compendial specifications. Its bulk and flow properties make it ideally suited for optimal blend homogeneity and constant dose uniformity. Also, it avoids the concerns over lactose intolerance and use of materials with animal origin. Learn more about this new mannitol-based excipient and the benefits of using it in Dry Powder Inhalation formulations.

3. Taking Control of Sustained Drug Release


Controlled-release of oral solid formulations is an area of major interest as it enables better alignment of the performance of the final drug product to the therapeutic need. The benefits of controlled release include reduced dose frequency, greater patient convenience and increased compliance. In many cases, long-acting efficacy of the active pharmaceutical ingredient (API) is required. When selecting excipients for controlled-release formulations, drug manufacturers require options that deliver superior reliability and consistency

Solution

Several approaches are available for sustained-release formulations. Matrix systems are widely used because of their straight-forward and simple formulation process. In contrast to formulations with a release rate-controlling coating layer, a matrix formulation generally has a reduced risk for dose dumping and related side-effects.

A new functional excipient based on polyvinyl alcohol (PVA) with optimized particle size and properties was developed specifically for sustained release solid oral formulations. It provides consistent, sustained drug delivery over long release periods and is very well suited for direct compression processes due to very good compressibility. The fully synthetic nature allows for tight control of properties and a reliable batch-to-batch performance, thus supporting Quality by Design (QbD) approaches.

4. Improve API Stability with the Right Excipient


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Dosing Accuracy Considerations in Dry Powder Inhalation

Many factors in a drug formulation can have a negative effect on the stability of the API. Reduced API stability can result in reduced shelf life, reduced efficacy, or in the worst-case scenario, cause harm to a patient.

Solution

Choosing the right excipients can improve API stability in a solid dosage drug formulation. Learn how excipients can help protect APIs with stability challenges due to water or heat, impact of the granulation process, or browning due to reducing sugars and peroxide impurities.

5. Implement QbD with the support of Excipient Suppliers


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Improve API Stability with the Right Excipient

Pharmaceutical manufacturers are under increased pressure from health authorities worldwide to implement Quality by Design (QbD) principles for novel and generic drugs. While implementation of QbD enables increased control over product quality, it requires close collaboration with the excipient supplier to ensure control over critical parameters.

Solution

Excipient suppliers should work in partnership to support your QbD approach. Defining the design space requires QbD samples – they should be available, and if not, what are your options? This cooperation is then essential to obtaining control over critical parameters once defined. Learn more about how we can help support your QbD initiatives.

6. Use Direct Compression to Improve Manufacturing Efficiency


Implement QbD with the support of Excipient Suppliers

Wet granulation is the most commonly used technology for the manufacture of tablets for oral medication. However, direct compression is gaining popularity among oral solid dose manufacturers because it is a time-saving process with fewer manufacturing steps. When should you use this newer methodology for mixing ingredients in a final formulation?

Solution

Learn about the benefits of direct compression tableting technology, when to use and and how to optimize a formulation for good manufacturing efficiency and better yield.

7. Enhance Solubility with Hot Melt Extrusion


Approximately 40% of marketed drugs and roughly 60% of drugs in development exhibit poor solubility, limiting their therapeutic efficacy and clinical prospects. New technologies are required to improve solubility to enable manufacturers to bring next generation therapeutics to the market.

Solution

API water solubility can be improved using hot melt extrusion (HME). In this process, the API is dispersed within a matrix polymer through heating and mixing. The resulting amorphous solid dispersion - with the API incorporated in its stabilized amorphous state - exhibits enhanced API dissolution properties and apparent solubility. Explore an excipient grade of polyvinyl alcohol specifically designed for HME.