Inside drug development: The fundamental principles of pharmaceutical formulation

Below, we break down each of the three categories mentioned above and explore how various considerations like release profile, dosage form, and excipient choice contribute to the final drug product’s success as a commercially produced therapeutic.

Molecular considerations for drug formulation

• Bioavailability: How effectively a drug is absorbed and utilized by the body after it’s administered through a specific route, such as oral ingestion, injection, inhalation, or topical application. Bioavailability depends on factors like drug solubility and the presence of excipients.

• Release profile: The release profile refers to the pattern or rate at which a drug is released from its dosage form into the bloodstream or target tissue. It describes how quickly and to what extent the drug becomes available for absorption and distribution after administration.

• Pharmacokinetics: Pharmacokinetics attempts to summarize what the body does to an API, such as how it absorbs, distributes, metabolizes, and eliminates a drug. Drug formulations may be designed to modify these important processes to achieve specific therapeutic goals.

• Particle size and crystallinity: The size and structure of drug particles can impact the bioavailability and solubility of the API, which can also impact dissolution and absorption rates. Smaller particle sizes and specific crystal forms can enhance a drug product’s performance.

• pH and ionic strength: The pH of a drug measures its acidity or alkalinity, and it can affect a drug’s stability, solubility, and how it interacts with the body. Ionic strength is a measure of the concentration of ions and can influence the drug’s solubility, stability, and delivery.

Patient-centric drug formulation considerations

• Dosage form: The physical form in which a drug is administered, such as tablets, capsules, liquid suspensions, creams, ointments, or injections. The choice of dosage form depends on factors like patient preference, route of administration, and the drug's chemical properties.

• Route of administration: The way in which the drug is introduced into the body, e.g., oral, intravenous, topical, or inhalation. The route of administration affects the drug's bioavailability and therapeutic effectiveness and can also impact the patient experience of taking a drug.

• Taste and odor: In the case of oral formulations like liquid suspensions, the taste and odor of the drug can affect the overall patient experience of taking it. Masking or modifying these characteristics may be necessary, especially for specific patient populations such as children.

• Color and appearance: The color and appearance of a drug formulation can influence patient perception and compliance. They may also serve as branding elements for the eventual drug product, so they should be carefully considered during the early formulation stages.

• Compatibility with other medications: For combination therapies, it’s important to ensure that the drug formulation is compatible with other drugs that may be administered simultaneously. Additionally, it’s essential to recognize any type of drug interaction that may impact patients.

Finished drug product considerations

• Excipients: Inactive ingredients, or excipients, in drug formulations serve various functions, such as binders, fillers, lubricants, preservatives, and dye. They play a crucial role in drug formulation to ensure proper dosage form and delivery and can also help to enhance shelf life.

• Stability: The ability of a drug formulation to maintain its quality and effectiveness over time. Factors such as temperature, humidity, and light can affect stability, therefore drugs must be formulated in a certain way to address and overcome degradation challenges.

• Dose strength: The amount of API, or drug substance, in a single dosage unit. Dose strength is determined by several factors such as therapeutic needs and patient population. For example, dose strength for children will typically be less potent than dose strength for adults.

• Packaging and storage conditions: Proper packaging and storage conditions are crucial to maintaining the stability and safety of the drug over its shelf life. For example, if an API is sensitive to UV light, it should be packaged in a carrier that’s impenetrable to such factors.

• Regulatory and quality standards: Compliance with regulatory guidelines and quality standards is essential to ensuring a drug formulation’s safety, efficacy, and consistency. Formulation is a key component of the drug development process and must meet regulatory standards.

“Drug formulations address practical concerns like patient compliance, making medications easier to administer, and increasing adherence to prescribing protocols.”

Drug formulation is an essential step in drug development, as it directly impacts the safety, efficacy, and patient experience of taking a drug. A well-crafted formulation ensures the APIs are delivered as intended, helping to optimize their therapeutic efficacy while minimizing side effects. Additionally, drug formulation helps to address practical concerns like patient compliance, making medications easier to administer, and increasing adherence to prescribing protocols. Additionally, it also plays a vital role in obtaining regulatory approval and patent protection, which underlines its significance in bringing new and improved therapies to market. In essence, the formulation process serves to bridge the gap between scientific breakthroughs and real-world applications, ultimately determining the impact of pharmaceutical interventions.

Given its overwhelming importance, many biopharma companies choose to partner with contract development and manufacturing organizations (CDMOs) for pharmaceutical formulation. CDMOs with years of experience can provide unparalleled industry knowledge and state-of-the-art equipment to pharmaceutical formulation projects. Moreover, collaborating with a CDMO can significantly reduce the financial burden associated with maintaining in-house formulation capabilities, allowing biopharma companies to allocate their resources toward other activities like research, clinical trials, and marketing. Quality partnerships between biopharma companies and CDMOs not only ensure reliable pharmaceutical formulation, but they also help to optimize the entire drug development journey, ultimately bolstering the biopharma company’s speed to market and competitive edge in a highly dynamic market.