Oral solid dose (OSD) drugs
are pharmaceutical preparations for oral administration in tablets, capsules, powders, or granules. They are mainly prescribed due to their convenience, ease of administration, and long shelf-life, and they continue to experience steady market growth.
This growth is largely attributed to the route’s ease of use, as well as increasing demand for generic drugs, since lower manufacturing costs make OSDs the most commonly prescribed generic dosage form.
OSD Formulation Development
Drug formulation for oral dosages identifies the appropriate manufacturing process to combine active pharmaceutical ingredients (APIs) with excipients in a manner that ensures the final drug product functions as intended.
Drug discovery and development is expensive and has one of the highest product failure rates in the world (less than 10% of drugs in Phase I clinical trials will become approved medicines). Formulation development plays a pivotal role in minimizing drug candidate failures.
How?
Cultivating a thorough understanding of the compound’s physical, chemical and mechanical properties in order to develop the ideal solid dosage helps ensure its performance, safety and viability from a manufacturing standpoint.
Types of oral solid dosage forms (OSDs)
- Tablet: These powdered medicines are compressed into a solid tablet form. They can be formed into different shapes and colors. Tablet drugs offer ease of manufacturing, stability, cost-effectiveness, and patient preference which then aids in patient compliance. Generally, tablet drugs offer a combination of benefits, including ease of use, an ability to split or cut the dose, excellent shelf stability and lower manufacturing cost.
- Capsule: These are medications that are either encapsulated or coated. They can contain powdered or liquid medicines. Capsules are increasingly popular due to their flexibility, lower risk of cross-contamination, suitability for sensitive drugs and ability to combine multiple non-compatible active ingredients together in a single dose.
- Orally dissolving tablet (ODT): This solid oral dosage form disintegrates quickly in the mouth without the need for a liquid. They are designed to dissolve faster in the saliva, allowing for rapid absorption of the active ingredient. ODTs may have higher bioavailability and an earlier pharmacological effect than traditional tablets.
- Immediate-release tablet or capsule: These tablets release the drug immediately after being taken once it reaches the gastrointestinal tract.
- Sustained release tablet or capsule: These drugs are released slowly and consistently over time. They typically consist of two components: the active ingredient(s) and a special coating that controls the rate at which medication is released.
- Effervescent tablet: These tablets are usually added to water, releasing carbon dioxide to form an effervescent solution. The benefits of this route of administration include their ease of use and fast-acting nature. Because the medication is simply dissolved in water, it can be absorbed by the body more quickly than other forms of medication.
OSDs: Robust Drug Formulation is Indispensable
Pharmaceutical formulation – mixing active drugs with other required components to achieve the appropriate solubility, particle size, polymorphism and more – is a critically important step in oral solid dose drug development.
The formulation and manufacturing of OSDs requires careful consideration of a wide range of factors:
- chemical and physical properties of the drug
- therapeutic indication
- patient characteristics
- manufacturing process
Ultimately, much of the formulation comes down to choosing the right excipients to improve drug stability and bioavailability, enable feasible manufacturing, and avoid drug and chemical interactions.
Importance of Excipient Selection
Excipients – inactive or slightly-active ingredients – comprise up to 90% of a medication. Their selection impacts a wide range of factors, from solubility (and thus bioavailability) to shelf life to manufacturing process design. Excipient selection focuses on developing a deep understanding of potential drug-excipient interactions, whether chemical, physical, physiological or otherwise, that could impact the stability or efficacy of the drug.
Key Considerations During OSD Formulation Development
Formulation development is critical to overcoming the challenges which can arise during drug development. Key characteristics include pH, polymorphism, solubility, and particle size, which impact stability and bioavailability – two important traits at the heart of formulation development.
- Stability
Ensuring stability is one of the primary challenges in oral solid dose drug formulation. Generally, drug stability refers to the degree to which a substance or product maintains the same properties and characteristics during its manufacturing, within specified limits, as well as throughout its storage and usage period.Most drugs are chemically unstable and may not maintain their properties over time, leading to reduced efficacy and potential toxicity. Therefore, manufacturers must consider the drug’s chemical and physical properties and choose relevant excipients to enhance drug stability. Stability studies are commonly used to ascertain the impact of humidity, temperature, light and other variables on the drug in order to determine whether degradation products (unwanted chemicals) have formed which might effect the safety or efficacy of the drug.
- Bioavailability
Bioavailability is another challenge in oral solid dose formulation. During OSD drug formulation and manufacturing, drug absorption is an essential factor drug sponsors or their development partners must consider. Most medications (reportedly as high as 70-80%) have poor solubility and low permeability, making it difficult for them to be absorbed into the body. Thus, pharmaceutical companies must choose relevant excipients and solubility enhancement processes that work in concert to increase drug solubility and permeability. - Drug Loading
The physical volume of a drug substance in a drug formulation can also create complications. Maintaining a suitable ratio of the drug substance (known as “drug loading”) to the overall dose can avoid flow problems in manufacturing systems or issues with homogeneity. - Scale-up
The scalability of a manufacturing process has an outsized impact on a drug’s success. Drug formulation continues across the drug development cycle, since what works at smaller scales (e.g., Phase I clinical) may be insufficient or impractical at commercial scales. For this reason, formulation development scientists must reexamine their understanding of processes and what occurs with the drug compound at each step-up in scale. This includes a thorough understanding of critical process parameters (CPPs) and critical quality attributes (CQAs), which guides selection of equipment and process steps.
An Emphasis on Formulation Expertise
Successful formulation development is highly dependent on the team’s knowledge and expertise. Prior experience with excipients – namely, their compatibility, functionality and physiochemical properties – is essential. Chemical process knowledge and scale-up are equally important competencies, alongside analytical testing, stability testing, GMPs, regulatory support & documentation as well as dose-specific know-how, such as sustained release formulation.
OTC Drug Formulation
We recently discussed some of the benefits of formulation prior to OTC manufacturing, though not all OTC commercialization projects have embraced it. Most reluctance stems from cost concerns. Since they are often lower-margin products, a drugmaker may be less willing to pay for formulation development when transferring or launching manufacturing via a new CDMO. But there are some compelling reasons why it has become a popular service request among OTC brands – read our earlier post on OTC drug formulation.
LGM OSD Capabilities: Hitting Your Milestones to Enhance Speed-to-Market
When it comes to outsourcing your molecule for OSD formulation development, drugmakers need a CDMO partner with a track record of regulatory approvals and successful commercial launches. Robust formulation development can shorten time-to-market, result in significant cost savings, and avoid the need for significant process changes or product rework in the future.
LGM Pharma has the facilities and expertise to formulate your next OTC, generic or innovator drug using Quality by Design (QbD) principles to ensure patient safety, efficacy, and compliance while meeting your timelines, budgets, and business requirements. We’ve invested heavily in state-of-the-art technologies and labs and can formulate and manufacture virtually any solid dose delivery system – whether a simple tablet or a more complex solid dosage form.
LGM Pharma is a proven contract development and manufacturing organization (CDMO) partner for your next orally ingested therapeutic with commercial batch sizes of up to 2+ million solid doses annually.
Contact us to discuss your OSD formulation needs.