Analysing the Efficacy of Oral Drug Formulations following Bariatric Surgery -The Crucial Role of Artificial Gastric and Intestinal Fluids in Drug Development.
In pharmaceutical R&D, understanding how a drug dissolves and is absorbed within the human body is essential for ensuring its efficacy and safety.
The complex formulation of artificial gastric and intestinal fluids plays an essential role in simulating human physiological conditions during in-vitro dissolution testing. These formulations are used when considering several specific patient populations, such as those who have undergone bariatric surgery, which can significantly alter gastrointestinal (GI) physiology.
The Importance of Artificial Gastric and Intestinal Fluids
Artificial gastric and intestinal fluids are meticulously designed to replicate the chemical composition and physical properties of human digestive fluids. This includes the correct pH levels, enzymes, and other substances that aid in the dissolution and absorption of drugs. The role of these artificial fluids is critical in mimicking the GI environment during dissolution testing, allowing researchers to understand better how drugs behave under specific conditions and ensuring that a drug will dissolve effectively once ingested.
Pickering Laboratories specializes in the preparation of high-quality artificial gastric and intestinal fluids for accurate dissolution testing. Pickering’s simulated Intestinal Flui
d and simulated Gastric Fluid test solutions are prepared according to USP specifications.
They are prepared with and without enzymes to accommodate different USP testing requirements. Their 2-part formulations come with dry pre-weighed enzyme powder to be mixed in before use. This allows for longer, room temperature, shelf life and predictable activity of the enzyme in solution.
Artificial Fluids and Drug Development: Impact on Product Dissolution
Simulating Gastric and Intestinal Conditions: The formulation of artificial gastric and intestinal fluids is not only about recreating normal physiological conditions but also about understanding how factors like gastric pH, enzyme concentration, and other components interact with drugs. For example:
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Gastric Fluids: The pH in the stomach typically ranges from 1.5 to 3.5, which is highly acidic. Artificial gastric fluids are designed to replicate this environment, ensuring that drugs that require an acidic environment for dissolution are tested under the correct conditions.
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Intestinal Fluids: The pH in the small intestine ranges from 6 to 7.5, and artificial intestinal fluids are formulated to simulate these conditions, as well as the presence of pancreatic enzymes. This is particularly important for solubilization and proper dissolution.
- Ensuring Quality Control: In-vitro dissolution testing using artificial fluids is a critical step in quality control, providing consistent, reproducible data on the release rate and bioavailability of a drug. Regulatory bodies like the FDA require dissolution testing as part of the approval process for new medications, and the use of well-formulated artificial fluids ensures that these tests reflect real-world conditions as closely as possible.
Example: Impact of Bariatric Surgery on the Efficacy of Oral Contraceptives
While oral contraceptives remain a highly effective form of birth control for many individuals, understanding how their efficacy following bariatric surgery can be compromised is imperative. Reduced gastric acid, altered transit time, and bypassing of sections of the small intestine can all interfere with their absorption, leading to reduced bioavailability and potentially increasing the risk of unintended pregnancies.
Key Factors Impacting Oral Contraceptive Efficacy Post-Surgery ![]()
- Changes in Gastric pH and Absorption: After bariatric surgery, gastric acid output is reduced, which alters stomach pH. Many oral contraceptives (especially combination pills) are designed to dissolve and be absorbed in a specific acidic pH. With reduced gastric acidity, the dissolution and absorption of oral contraceptives may be impaired, leading to potentially lower concentrations in blood. This can reduce the effectiveness of the contraceptive, increasing the risk of unintended pregnancy.
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Altered Gastrointestinal Transit Time: Bariatric surgery often leads to faster gastric emptying and reduced time drugs spend in the stomach and small intestine. For oral contraceptives, this reduction potentially lowers bioavailability. Therefore, faster gastric emptying might not allow the contraceptive enough time to dissolve fully and be absorbed into the bloodstream
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Bypassing of the Duodenum and Jejunum: In procedures like Roux-en-Y gastric by-pass surgery (RYGB), part of the small
intestine, including the duodenum and jejunum, is bypassed. These areas are crucial for the absorption of many oral medications, including some components of oral contraceptives. With less surface area for absorption, there may be reduced efficacy of the drug, especially for individuals relying on standard oral contraceptive formulations.
ESSLAB – How can we assist your analytical processes.
ESSLAB has established itself as a go-to specialist supplier offering high-quality biorelevant artificial fluids, Certified Reference Materials (CRMs), and sample preparation materials. ESSLAB have developed a reputation as a trusted supplier and a primary partner of Pickering Laboratories. We work closely with leading manufacturers to providing a comprehensive, high-quality range of instrumentation and materials designed to enhance the accuracy and efficiency of drug development and quality control processes.
*United States Pharmacopeia