Advances in Oral Drug Delivery Systems.pptx

Chalanges and Opportunities

1. Advances in Oral Drug Delivery Systems: Challenges and Opportunities A Comprehensive Review

2. Introduction Oral administration : Most preferred route for drug delivery due to convenience and non- invasiveness . Challenges : Harsh gastrointestinal (GIT) environment , physiological barriers , and low bioavailability . Innovative approaches : Nanoparticulate formulations , biomimetic drug formulations , microfabricated devices .

3. Biological Barriers to Oral Drug Delivery Drug delivery via oral route faces anatomical, biochemical, and physiological barriers in the GIT. To optimize drug targeting and bioavailability through innovative pharmaceutical approaches.

4. Anatomical Barriers GIT Anatomy : Oral cavity, esophagus, stomach, small intestine, colon. Unique Barriers : Oral cavity : Limited surface area, presence of saliva and enzymes . Esophagus : Low permeability , short residence time . Stomach : Acidic environment , mucin-bicarbonate barrier . Small intestine : Large surface area but presence of digestive enzymes and bile salts . Colon : Higher pH , longer residence time , gut microflora .

5. Oral Cavity and Esophagus Oral Cavity : Barriers : Saliva, enzymatic composition , limited surface area. Advantages : Mild microenvironment , good drug permeability . Esophagus : Challenges: Low permeability, short drug residence time. Focus: Not a primary target for drug delivery.

6. Stomach Stomach Environment : pH Range : 1.0–2.5, strong acid environment . Barriers : Gastric mucin-bicarbonate barrier , extrinsic epithelial cells , tight junctions , pepsins . Impact : Degradation of acid-labile drugs , limited drug absorption .

7. Small Intestine Small Intestine Characteristics : Surface Area: Extensive due to villi and microvilli . Prime site for oral drug delivery : Tremendous surface area, diverse transport routes . Challenges : Pancreatic enzymes , bile salts , mucosal layer, and the need for increased retention time .

8. Colon Colon Environment : pH : Higher compared to the upper GIT. Residence Time : Longer , facilitating sustained drug release . Enzyme Activity : Lower compared to the small intestine . Microflora : Significant role in drug metabolism , potential for targeted drug delivery .

9. Biochemical Barriers pH Variation : Gradient: Acidic in the stomach to alkaline in the colon (pH 1 to 8). Impact: Drug activity and bioavailability affected by pH. Digestive Enzymes : Role: Critical influence on drug stability and bioavailability. Location: Predominantly in the stomach and small intestine.

10. Physiological Barriers Low Permeability : GIT's barrier to foreign substances limits drug absorption. Mucus Barrier : Function: Restricts direct interaction of drugs with epithelial cells. Composition: Viscous gel of mucins and glycoproteins, forming a protective layer.

11. Applications of Oral Drug Delivery Systems Targeting Local GIT Diseases : Approaches: Gastroretentive , pH-dependent, and mucoadhesive systems. Targeting Local GIT Diseases : Approaches: Gastroretentive , pH-dependent, and mucoadhesive systems.

12. Local Targeting to GIT Gastroretentive Systems : Strategy: Prolong gastric residence time for drugs absorbed or acting in the stomach/upper GIT. Small Intestine Targeting : Methods : pH-responsive formulations , mucoadhesive strategies . Colon Targeting : Techniques : Prodrugs , enzyme-responsive and pH-dependent systems .

13. Gastroretentive Systems Strategies : Floating, expandable, and mucoadhesive formulations. Benefits : Prolonged drug residence time, sustained or controlled drug release, reduced systemic concentration fluctuations.

14. Examples of Gastroretentive Systems Pramipexole-Loaded Nanofibers : Design: Self-inflating effervescence-based electrospun nanofibers . Function : Floating in stomach fluid , prolonged gastric residence . Gabapentin-Loaded Expandable Formulation : Mechanism : Unfolds in the stomach to control drug release . Simvastatin-Loaded Mucoadhesive System : Material: Thiomers enhancing gastric retention .

15. Small Intestine Targeting pH-Responsive Formulations : Composition : Coatings or matrices sensitive to pH changes . Function : Prevent drug degradation in acidic stomach , enable release in the intestine . Mucoadhesive Formulations : Strategy : Extend contact time with intestinal mucosa . Examples : Intestinal patches .

16. Colon Targeting Prodrugs : Design: Inactive in the upper GIT, activated by colonic enzymes . Examples : 5-ASA derivatives like sulfasalazine and olsalazine . Enzyme-Responsive Systems : Approach : Polymers sensitive to colon-specific enzymes . Examples : Polysaccharide-based formulations .

17. Increased Bioavailability Nanoparticles : Benefits : Protect drugs from GIT environment , enhance absorption . Types : Liposomes , microspheres , nanocomposite carriers . Microfabricated Devices : Innovations : Devices like luminal unfolding microneedle injector (LUMI).

18. Examples of Increased Bioavailability Nanocomposite Carriers for Infliximab : Function : Enhanced targeted delivery for inflammatory diseases . Coated Nanocomplexes for Insulin : Design: pH-dependent release , improved drug absorption . Calcium Phosphate Nanoparticles for Vaccines : Application : Oral delivery of protein antigens .

19. Targeting Delivery for Non-Gastrointestinal Diseases Challenges : Overcoming harsh GIT environment to target systemic diseases . Innovative Strategies : Biomimetic systems , yeast-derived capsules .

20. Systemic Inflammation Targeting siRNA Particles ( GeRPs ) : Composition : β1,3- D- glucan based . Function : Target macrophages and dendritic cells , reduce inflammation . Yeast-Derived Capsules : Mechanism : Bioinspired ‘ Trojan horse ’ strategy for delivering anti- inflammatory drugs .

21. Tumor Targeting Yeast Biomimetic System : Application : Oral chemotherapy . Example : Cisplatin delivery via yeast-derived capsules . Autonomous Oral Nanoparticles : Innovation : Self-assembly in the intestine for drug delivery .

22. Obesity-Related Diseases Targeting Bindarit-Loaded Nanoparticles : Modification : Laminarin coating . Function : Target multiple lesions like adipose tissue , fatty liver . Yeast Microcapsules : Delivery : IL-1b shRNA for reducing obesity in mice .

23. Gut-to-Brain Drug Delivery Noninvasive Prodrug Approach : Design: Conjugation with β- glucans for crossing the IEB and BBB. Target: Gliomas . Mechanism : Lymphatic transport and macrophage-mediated delivery .

24. Cardiovascular Disease Targeting Biomimetic Yeast-Derived Microcapsules : Function : Target aortic plaques in atherosclerosis . Advantage : Prolonged retention and targeted drug delivery .

25. Conclusion Advances in Technology : Innovative approaches improving the effectiveness of oral drug delivery systems. Future Research : Focus on overcoming existing barriers to enhance drug targeting and bioavailability. Outlook : Continued development of novel delivery systems for a broad range of diseases.