PLGA (poly lactic co glycolic acid )

Dosage form design

1. Biodegradable carrier PLGA Poly Lactic-co-Glycolic Acid 1

2. Contents : Introduction on biodegradable polymers PLGA Overview Physico -chemical Properties Pharmacokinetics and Bio-distribution Profile Copolymers of PLGA 2

3. Biodegradable Polymers are natural or synthetic in origin and are degraded in vivo, either enzymatically or non-enzymatically or both . Our mission to produce : biocompatible, toxicologically safe by-products which are further eliminated by the normal metabolic pathways INTRODUCTION B iocompatibility is not an intrinsic property of a material, but depends on the biological environment that exists with respect to specific drug-polymer-tissue interactions 3

4. A mongst all the biomaterials , application of the biodegradable polymer poly lactic-co-glycolic acid (PLGA) has shown immense potential as a drug delivery carrier and as scaffolds for tissue engineering PLGA are a family of FDA-approved biodegradable polymers that have been extensively studied as delivery vehicles for drugs , proteins and various other macromolecules as DNA,RNA and peptides 4 PLGA It’s most popular !!!!!!!! because of its long clinical experience , favorable degradation characteristics and possibilities for sustained drug delivery It’s possible to tune the overall physical properties of the polymer-drug matrix by controlling the relevant parameters to achieve a desired dosage.

5. PLGA is a Copolymer of Poly lactic acid (PLA) + poly glycolic acid (PGA ) Poly Lactic acid has an Asymmetric carbon .Typically described D or L as ( PDLA)/ (PLLA) * Generally PLGA contains poly D,L lactic acid -co- glycotic acid where D and L forms are in equal ratio. ! Hydrolysis of ester bond in water Presence of methyl side groups in PLA : makes it more hydrophobic than PGA so lactide rich PLGA copolymers are less hydrophilic , absorb less water subsequently degrade more slowly

6. PLA T he polymer PLA can be made in highly crystalline form(PLLA ) or completely amorphous (PDLA) due to disordered polymer chains PGA PGA is void of any methyl side groups and shows highly crystalline structure in contrast to PLA PLGA Can be processed into almost any shape and size, and encapsulate molecules of any size PC Ps I t is essential to understand the physical , chemical and biological properties of PLGA to design a better controlled drug delivery device 6

7. P arameters of the formulation can change with time, such as the glass transition temperature (Tg), moisture content and molecular weight . Which influences the release and degradation rates of incorporated drug molecules . Physical properties themselves depend upon multiple factors : 1)molecular weight, 2)the ratio of lactide to glycolide , 3)the size of the device, 4)exposure to water 5)storage temperature Due To Hydrolysis of PLGA 7

8. Degree of crystallinity and melting point of the polymers are directly related to the molecular weight of the polymer As a rule, higher content of PGA leads to quicker rates of degradation with an exception of 50:50 ratio of PLA/PGA, which exhibits the fastest degradation The Tg (glass transition temperature) : are reported to be above the physiological temperature of 37 C SO they are glassy in nature , thus exhibiting fairly rigid chain structure Tg decrease with a decrease of lactide content in the copolymer composition and with a decrease in molecular weight 8

9. 9 Pharmacokinetics and Bio-distribution Profile

10. Biodistribution and pharmacokinetics of PLGA follows a non-linear and dose-dependent profile !!!!!!!! 10

11. B oth blood clearance and uptake by the mononuclear phagocyte system (MPS) may depend on dose and composition of PLGA carrier . FACT

12. 12 To address these limitations: studies have investigated -)the role of surface modification , By incorporation of surface modifying agents … Blood circulation half life increases . The degradation of the PLGA carriers is quick on the initial stage (around 30%) and slows eventually to be cleared by respiration in the lung

13. For better delievery formulations block copolymers of polyesters (PLGA) and PEG were made - PLGA is hydrophobic WHILE - PEG is hydrophilic . Copolymers of PLGA Block copolymer are either : 1) Diblock copolymer (PLGA-PEG) 2)Triblock copolymer (PLGA-PEG-PLGA, ABA) & (PEG-PLGA-PEG, BAB) 13

14. Before continuing What is temperature responsive copolymers HOW

15. Diblock copolymer Triblock copolymer PEG chains orient themselves towards the external aqueous phase in micelles ,surrounding the encapsulated species Hydrophobic PLGA form associative crosslinks & hydrophilic PEG allow the copolymer molecule to stay in solution. PEG layer act as barrier , reducing interaction with foreign molecules by steric & hydrated repulsion , enhancing shelf stability Temperature responsive copolymers . ABA & BAB are thermogel , free flowing solution at low temp. & high viscous at body temp . Yet , addition of PEG reduces encapsulation efficiency for drugs . The exact mechanism is unclear however that could be because steric interference of drug-polymer interaction by PEG chains . Drug release from both ABA & BAB by 2 mech . : 1)Drug diffuse from hydrogel during the initial release phase 2) Erosion of hydogel matrix in later phase shows better release kinetics from formulation than PLGA alone During degradation of BAB : there is mass loss of PEG-rich components ,that increasing hydrophobicity of remaining gel ( causing less water content ) Copolymers Diblock Copolymer and triblock copolymer 15 That can be applied to other copolymer combinations , eg . PLGA & polycaprolactone

16. To Sum up What are the types of polymers What is PLGA What does the methyl grp in PLA Does What happen to the formulation parameters due to hydrolysis of PLGA What do the physical properties depend on higher content of PGA leads to PK And BD of PLGA follows what profile PLGA Accumulate in What is the role of surface modification What are the types of copolymers Compare between bi/triblock copolymers 16

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