Solid Formulation Strategies

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, concerns for lactose intolerance in patients, and the use of an excipient of animal origin.

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. It also avoids the concerns over lactose intolerance and use of materials with animal origin.

Taking control of sustained drug release

Controlled-release of oral solid formulations enables better alignment of the performance of the final drug product to the therapeutic need. The benefits of sustained 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 sustained-release formulations, drug manufacturers require options that deliver superior reliability and consistency.

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.

Improving API stability with the right excipients

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.

Choosing the right 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.

Using direct compression to improve manufacturing efficiency

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 steps. Manufacturers should consider the benefits of direct compression tableting technology for mixing ingredients in a final formulation, as well as how to optimize their formulation for good manufacturing efficiency and better yield.

Enhancing 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. Solubility of APIs 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. Manufacturers can now make use of an excipient grade of polyvinyl alcohol specifically designed for HME.