factors influencing GIl absorption of the drug

The absorption of drugs in the gastrointestinal (GI) tract is influenced by several interrelated factors. Physicochemical properties of the drug, such as solubility, permeability, and ionization state, play crucial roles. Drugs must dissolve in the aqueous environment of the GI tract to be absorbed effectively, with lipophilic drugs generally having higher permeability. The characteristics of the GI tract itself also impact absorption; the small intestine, due to its extensive surface area with villi and microvilli, is the primary site for efficient absorption compared to the stomach or large intestine. Factors like gastric emptying rate, affected by food and liquids, and GI transit time, which can vary widely among individuals, further influence drug absorption kinetics. Interactions with other substances, including food, beverages, and concurrent medications, also play significant roles. For instance, food can alter gastric pH and affect drug solubility, while drug interactions with excipients in formulations can modify absorption characteristics. Patient-specific factors such as age, presence of GI diseases, and genetic variability in drug metabolizing enzymes and transporters contribute to individual variations in drug absorption. Understanding these multifaceted factors is essential for optimizing drug formulations and dosing regimens to achieve desired therapeutic outcomes effectively.

1. Factors influencing GI absorption of the drug Presented by- Hatasha Vaddadi Enrolment number- 2308422110004 M. Pharm (pharmaceutics), 2 nd Sem

2. Contents Introduction Factors influencing GI absorption absorption Physicochemical factors Dosage form and formulation-related factors. Patient-related factors Conclusion

3. Introduction to Bioavailability and Absorption Bioavailability refers to the amount of a drug that is able to reach the systemic circulation and have a therapeutic effect. Absorption is the process by which a drug is taken up from the gastrointestinal (GI) tract and enters the bloodstream. Understanding the factors that influence GI absorption is crucial for optimizing drug delivery and efficacy.

4. Factors Influencing GI Absorption of a Drug 1 Physicochemical Properties The drug's solubility, lipophilicity, ionization state, and molecular size can impact its ability to permeate the GI membrane. 2 Dosage Form The formulation and delivery system of the drug can affect dissolution and release kinetics. 3 Patient Factors Individual differences in GI physiology, genetics, and disease states can alter absorption.

5. Physicochemical Properties of the Drug Solubility Drugs with higher aqueous solubility are generally more bioavailable as they can more easily dissolve and permeate the GI membrane. Lipophilicity Lipophilic drugs can more readily cross the lipid-rich GI epithelium, but may have poor water solubility. Ionization The ionization state of a drug can impact its solubility and permeability across the GI tract.

6. Dissolution rate It is the RDS for lipophilic drugs whereas drugs like neomycin have high aqueous solubility. Surface area Surface area and particle size are inversely proportional. An increase in the effective surface area leads to an improvement in dissolution rate. Salt form of the drug Enhances dissolution in biological fluids, leading to better absorption and bioavailability, crucial for effective drug delivery and therapeutic outcomes

7. Polymorphism and Amorphism Amorphous forms can improve drug dissolution and bioavailability, especially for poorly water-soluble drugs. Amorphous> metastable> stable Hydrates and solvates Hydrates are crystalline forms of a compound that contain water molecules in their crystal lattice. Solvates are solvent molecules incorporated into the crystal lattice. Solvates > hydrates

8. Dosage Form and Formulation Related Factors Dissolution The rate and extent of drug dissolution from the dosage form can affect absorption. Drug Release Controlled-release formulations can alter the kinetics of drug release and subsequent absorption. Excipients Inactive ingredients in the formulation can influence solubility, permeability, and absorption. 1 3 2

9. Dissolution time The duration it takes for a solid substance to dissolve completely in a liquid solvent under specific conditions. Manufacturing variables Manufacturing processes influence drug dissolution from solid dosage forms. Product age and variables. Aging and storage conditions can affect the solubility and absorption. 4 5 6

10. Patient Related Factors Gastric pH Changes in stomach acid production can impact dissolution and absorption of pH-sensitive drugs. GI Transit Time Faster or slower transit through the GI tract can affect the time available for absorption. Genetic Factors Genetic polymorphisms can influence expression of drug transporters and metabolizing enzymes.

11. Age Changes in stomach acid production can impact the dissolution and absorption of pH-sensitive drugs. Blood flow through GIT Faster or slower transit through the GI tract can affect the time available for absorption. Conditions like inflammatory bowel disease or liver disease can alter GI absorption. Disease state

12. Conclusion 1 Optimize Absorption Understanding the key factors that influence GI drug absorption is crucial for developing effective and safe pharmaceutical products. 2 Personalized Approach Considering patient-specific characteristics can help tailor drug therapy to individual needs and maximize therapeutic outcomes. 3 Continuous Research Ongoing research in this field will further elucidate the complex mechanisms governing GI drug absorption.

13. References Book - Biopharmaceutics and Pharmacokinetics a treatise by DM Brahamnkar and Sunil Jaiswal, second edition(2009)-page number 26-78 Bhutani P, Joshi G, Raja N, Bachhav N, Rajanna PK, Bhutani H, Paul AT, Kumar R. US FDA approved drugs from 2015–June 2020: a perspective. Journal of Medicinal Chemistry. 2021 Feb 22;64(5):2339-81. Varma MV, Kaushal AM, Garg A, Garg S. Factors affecting mechanism and kinetics of drug release from matrix-based oral controlled drug delivery systems. American Journal of Drug Delivery. 2004 Mar;2:43-57.