Challenges and opportunities in oral formulation development

Thanks to oral formulation, many drugs crucial for the health and well-being of millions of people can be administered and save countless lives. The field of drug formulation is in a constant state of innovation, creating a plethora of challenges to overcome, but also opening up a world of opportunities.


What is oral formulation?

Oral formulation is the development and manufacturing of pharmaceuticals designed for oral delivery. Drugs introduced to the body through oral delivery are absorbed by the stomach, intestine, or gastrointestinal tract. Common examples of oral drug delivery systems include tablets and capsules.


What is formulation drug development?

Drug formulation is the process of creating licensed pharmaceutical products. During drug formulation development, various types of drug molecules are combined to produce the drug’s active ingredients. The delivery method of a drug is also chosen during formulation.

Proper drug formulation requires that developers consider what method of delivery will be the less intrusive to the daily life of a patient. Oral formulation represents an efficient way for patients to self-administer drugs that must be taken periodically. Thanks to the creation of oral administration methods, drugs that must be taken several times a day can be easily provided to patients.

Other formulation approaches exist besides oral formulation. Examples of drug formulation development processes include:

  • Parenteral formulations: This type of formulation is responsible for the creation of substances meant to be administered through an intramuscular (IM), subcutaneous (SC), or intravenous (IV) injection.
  • Topical formulations: Creams, gels, ointments, and lotions designed for specific areas of the body and skin conditions are created via topical formulations.
  • Modified-release formulations: The purpose of this type of formulation is to create drugs that act over an extended period of time. The effects of these drugs are experienced at a slow but steady rate.
  • Novel drug formulations: Novel drug delivery systems attempt to enhance the integrity of patient health by implementing innovative formulation strategies.


Why is formulation important?

Drug formulation is extremely important for the pharmaceutical industry because it is the process that generates the appropriate preparation method and form of a drug. Proper drug formulation development guarantees that manufactured drugs are safe and accessible to consumers. Formulation plays a vital role in drug creation so it is in the best interest of pharmaceutical companies to devise practical and manageable drug formulation strategies as early as possible during the development process.

In a survey performed on behalf of Informa Pharma Intelligence, Rentschler Biopharma SE, and Leukocare AG, pharmaceutical experts were asked to evaluate the importance of the different factors in the drug development process. The research found that the general opinion is that drug formulation and the creation of unique product features are the most important and valued aspects of drug development (source).

For the pharmaceutical experts who participated in the study, drug formulation was more influential to the overall success of development than considerations about cost, time-to-market, API development, and other critical aspects. The strategic planning of drug formulation can give rise to significant economic and competitive advantages.


What are the challenges and opportunities in oral formulation development?


The stability of the physicochemical properties of a drug is one of the main challenges faced during drug formulation. Proper evaluation of a drug’s stability is required to improve the product’s quality, prevent toxicity, and increase both safety and efficacy. Several factors, such as environmental conditions, can hinder the integrity of pharmaceutical products. Stability research aims to reduce the chances of medicines becoming compromised, and in the process create more trustworthy products.

For instance, moisture could have an impact on the shelf stability of a drug. Stability research might show that moisture-induced aggregates can be reversed by adjusting the pH and introducing reducing sugars in the mixture. The final product of this research will therefore be better suited for transportation and distribution.


Bioavailability is the amount of a drug that is successfully absorbed by the body of a patient. A drug may have low availability because part of it may become inactive or have its properties changed once it enters the systemic circulation. It is possible that not all of a drug is properly absorbed, or that the metabolism of the drug occurs before reaching the area of the body where it is required.

Drug administration using an intravenous (IV) injection, for instance, has a bioavailability of 100% (excluding some exceptions). In the case of oral formulation, bioavailability is highly fluctuating. The absorption of oral drug delivery methods is affected in large part by a phenomenon known as first-pass metabolism.

First-pass metabolism happens when a drug metabolizes en route to its intended area of action. In the case of oral medication, this usually happens in the liver. Consequently, a person suffering from a liver condition may experience a bioavailability increase due to a malfunctioning liver being unable to affect oral immunization. Other organs where first-pass metabolism is commonly observed include the intestines and the lung adrenal glands.

Factors that can contribute to low bioavailability include:

  • Age
  • Sex
  • Physical activity
  • Genetics
  • Stress
  • Disorders like malabsorption syndromes and achlorhydria
  • Previous surgery such as bariatric surgery
  • Hydrolysis by gastric acid
  • Conjugation in the intestinal wall
  • Luminal microflora
  • Interaction with other drugs


Drug solubility is the ability of a pharmaceutical product to be dissolved in a liquid. A product is considered very soluble when it only needs a small amount of a solvent to dissolve. In contrast, a drug with low solubility requires thousands of times its weight in solvent before it dissolves. Solubility is one of the main factors affecting the bioavailability of drugs.

Low solubility leads to suboptimal drug efficiency, bad absorption, and an increased chance of side effects. Drugs administered by oral delivery have very low solubility, making solubility evaluation an indispensable procedure in the early stages of oral drug discovery. On that account, solubility enhancement has become exceedingly valuable in current oral drug formulation development.

Drug solubility is affected by four main factors:

  • pH Levels: The hydrogen content in a solution can affect its solubility. Strong pH in a solution can cause it to fully dissociate, while that will only partially happen with low pH solutions. If a drug substance is a stronger acid, then it dissociates in water with higher efficiency.
  • Polarity: Ionization is important for solubility and ion trapping is required for a drug to work properly. In order to be most effective, drugs must be non-ionized in the stomach or the intestines to be absorbed by the body. Drugs must regain an ionized status while in the bloodstream to prevent them from returning to the gastrointestinal tract. Lipid solubility benefits the absorption process.
  • Drug particle size: The size of drug molecules directly affects their solubility. Larger particles tend to be less soluble, especially if the solutes experience the same temperature, pressure, and polarity factors.
  • Interaction with the body: Due to most substances being endothermic, the process of dissolution causes pharmaceuticals to absorb heat. The rise in temperature when a drug enters the body can positively influence its dissolutive properties. The speed of solubility is also increased thanks to the agitation drugs encounter inside the body.

Safety of pediatric patients

A major challenge faced by the pharmaceutical industry is the lack of medication that is designed to be administered to children. Most approved drug formulations are not intended for use in pediatric patients, leading to health professionals having to prescribe adult formulations as off-label medications. Research provides evidence that off-label adult formulations can expose pediatric patients to potentially harmful excipients which happen to be essential ingredients in many medicines (source). Not only are pediatric patients exposed to toxicity, but they can also experience a series of harsh side effects.

The development and manufacturing of oral drug delivery methods for pediatric patients present a considerable opportunity for the creation of new products. Pediatric patients are a heterogeneous group, and the metabolism of newborn infants can’t be expected to function similarly to that of school-aged children. For this reason, future pharmaceutical products for pediatric use should be devised for patients at different stages of life.

Patent protection

Drug formulation patent claims are a delicate matter. Patents are vulnerable to attacks using the legal argument that formulations covered can be considered obvious because of their close relation to other formulations already known at the time their patent was filed.

Even if the features of a formulation were not explicitly advertised in a prior art, a legal court might still find the patented formulation obvious. Overcoming an obviousness challenge, however, can be done so with proper legal defense. On that account, besides following all the required legal procedures, patentees also have to be prepared to legally defend their products.


Drug development services

Developing a drug from the planning stages to its arrival on the market is a very complicated process. Test methods and formulations must be strategically planned to ensure the most efficient use of time and resources. Pre-clinical and clinical testing are complex but indispensable procedures to follow. Furthermore, patents and regulatory plans must also be taken into consideration.

By providing an integrated drug development service, Altus offers planning and execution strategies regardless of the developmental stage of a project. Pharmaceutical companies partnered with Altus can expect the process of taking a drug from the Lab to the market to be effortless.

Our team facilitates drug formulation development for First in Human studies. Altus manufactures the product batches necessary to conduct later clinical trials, including phase III trials. In addition, we can also arrange meetings with the appropriate regulatory authorities, helping companies cut through all the red tape needed for clinical testing and approval.

Drug development services