SOLID DISPERSION FILMS
Facile Innovative Technology
PROF. PADMA V. DEVARAJANDean-Research and Innovation, Senior Professor in Pharmacy and former Head, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology(Deemed University) Mumbai. E-mail: pv.devarajan@ictmumbai.edu.in
19-21, 2022
DISSO AMERICA2022 SEPTEMBER
SOLID DISPERSION API CAR RIE R + EXC IPIE NTS
CONVENTIONAL
FORMULATIONS
BCS CLASSIFICATION
SOLUBILIZATION SOLID DISPERSIONS
BCS IV
BCS II
BCS I
ADVANCED
ATGSDF ADVANTAGE
BIOENHANCEMENT
THIRD GENERATION SOLID DISPERSION ATGSDF FILM TECHNOLOGY ATGSDF BCS II/IV DRUG
FIRST GENERATION CRYSTALLINE SECOND GENERATION • POLYMERIC THIRD GENERATION • POLYMERS FOURTH GENERATION • POLYMERS SOLID DISPERSIONS IMMEDIATE RELEASE CONTROLLED RELEASE UREA SUGARS POLYMERS POLYMERS CUM SURFACTANTS POLYMERS, CUM SURFACTANTS CONTROLLED RELEASE POLYMERS BCS II/IV DRUGSBCS II DRUGS
CHALLENGES IN SOLID DISPERSIONS
ATGSDF A PROPOSED SOLUTION
ADVANCED THIRD GENERATION SOLID DISPERSION FILM ATGSDF POLYMER AS A FILM &
SELF MICROEMULSIFYING COMPOSITION (SMEC)
ADVANCED THIRD GENERATION SOLID DISPERSIONS
Is it an Oral Thin Film???
Indeed!! An Oral Thin Film with a twist !! It is wrapped around a core
ORAL THIN FILM MANUFACTURE
COATED TABLETS
ATGSDF SCHEMATIC
DISINTEGRATED DRUG FREE
CORE (<1 MINUTE)
DRUG LOADED
RELEASED IN SITU
FILM
Film wrapped around a core
FILM
ATGSDF
• ENHANCED SURFACE AREA
SMEC
•PLASTICIZATION
SMEC
RAPID
DISSOLUTION
SMEC ENHANCED PERMEATION
BIOENHANCEMENT
ADVANTAGE ATGSDF
Advanced yet simple technology
Based on time tested technology practiced in the pharma industry
combination of
AND
•
•
• Innovative
Solid dispersion Technology SMEDDS Technology OTF Technology SIMPLE
EFFECTIVE
ADVANCED THIRD GENERATION SOLID DISPERSION FILM OF CURCUMIN
Dr. Prashant Mande
VALIDATING THE ATGSDF
Mande PP, Bachhav SS, Devarajan PV. Solid dispersionof curcumin as polymericfilms for bioenhancement and improvedtherapy of rheumatoidarthritis.PharmRes 2016;33(8):1972 87.
THE METHOD
Solubility of curcumin in SMEDDS components (Oil/surfactant/cosurfactant)
Identifying SMEDDS region
Preparation of CUR-SMEC
Preparation and Evaluation of Polymeric flims with and without CUR-SMEC
ATDSDF of Cur by coating Polymeric solutions with and without CURSMEC In vitro and in vivo evaluation
CURCUMIN SOLUBILITY • Cur exhibited good solubility of greater than 25mg/mL in most components CapmulMCMCaptex300LabrasolTween80PropyleneGlycolSMEC TEC DBSS/Cos 0 20 40 60 80 Capmul MCM Captex 300 Labrasol Tween 80 Propylene Glycol SMEC TEC DBS S/Cos 45.72 27.2 71.43 43.31 26.85 42.14 3.85 2.11 30.56 Cur solubility mg/mL 14
Pseudo-ternary phase diagrams Capmul MCM
The globule size obtained with selected SMEC was between 100 and 120nm, confirming microemulsion formation
15
PREPARATION OF SELF MICROEMULSIFYING COMPOSITION (SMEC)
SMEC PG Tween 80 Capmul MCM 16 High curcumin solubility
COATING SOLUTION
FREE FILMS
• Polymers : Kollidon VA 64, HPMC,, Eudragit EPO and Eudragit RLPO, Soluplus • Drug: CURCUMIN • SMEC Components/Plasticizers • Solvent system: Acetone: water (80:20) FILM FORMATION • Casting • Films observed under fluorescence microscope using IF550 filter at 4x/0.13PhL lens (Olympus, Japan) 17
K VA
Unplasticized
FREE FILM STUDY
TEC DBS
SMEC
Smooth and uniform films with SMEC with no crystallization Crystallization of Cur seen with TEC and DBS
HPMC
Soluplus EPO RLPO
18
ATGSDF
Simple & Innovative
19
ATGSDF
Simple & Innovative
WATER
CUR- ATGSDF
Cur SMEC-SDs film after disintegration of tablet
➢IPA-ACG SCITECH INNOVATION AWARD 2017
20
SCANNING ELECTRON MICROSCOPY (SEM)
A B C D E F
✓ Cur SMEC-SD (KSM20) revealed smooth, homogenous and uniform films with no evidence of Cur crystallization. ✓ Cur SD (KSM0) revealed crystals of with cracks on the film. 21 CUR SMEC-SD CUR - SD
CONTACT ANGLE Inertcore KSM0KSM20HSM20EPSM20SSM20RLSM20 0 50 100 150 Inert core KSM0 KSM20 HSM20 EPSM20 SSM20 RLSM20 78 129 7 14 15 24 27Contact angle (Degree) 22 SIGNIFICANTLY LOW CONTACT ANGLE
IN
RELEASE
of polymer
Effect of SMEC/plasticizer
VITRO DRUG
• Kollidon SR (KSR) as polymer • t50% 6.45min and • t90% 28.45min • Significantly slower release with other polymers 23 KSR with SMEC significantly faster release Effect
IN VITRO DRUG RELEASE
of surface area
Effect of barrier coat
24
Surface area can be modified to tailor drug release and drug loading Effect
F2 value 74.25 Barrier coating did not affect release
ADVANTAGE ATGSDF-CUR
O ALL CUR SMEC SDS
REVEALED MICROEMULSION
FORMATION IN DISSOLUTION
WITH GLOBULE SIZE IN
RANGE OF
MEDIA
THE
100-115NM AND PDI < 0.3.
PHARMACOKINETIC STUDY
26
plantar injection of 0.1 ml of CFA in the
PHARMACODYNAMIC STUDY Rheumatoid arthritis Model
Organ removal for Histopaths
27 Day1 Day7 Day14 Day21 Sub
left hind paw Body Weight & Paw Vol. measurement Daily oral dosing of Test and Standard formulation (10mg/Kg/day)
RADIOGRAPHY
ATGSDF-CUR COMPARABLE TO INDOMETHACIN
28
REDUCTION IN SYNOVIAL JOINT SWELLING
(A) Normal rats (B) Arthritic control (C) IND (D) Plain Cur (E) Cur SDs (F) Cur SMEC-SDs 29 ATGSDF-CUR COMPARABLE TO INDOMETHACIN
C-REACTIVE PROTEIN AND RHEUMATOID FACTOR
ATGSDF-CUR COMPARABLE TO INDOMETHACIN
30
LIVER HISTOPATHOLOGY
Indometha cin Liver toxicity
Liver toxicity
31 ATGSDF-CUR No
(A) Normal rats (B) Arthritic control (D) Plain Cur (E) Cur SDs
ADVANCED THIRD GENERATION SOLID DISPERSION FILM OF TADALAFIL
Dr. Prashant Mande
VALIDATING THE ATGSDF
Mande PP, Bachhav SS, Devarajan PV. Bioenhanced advanced thirdgenerationsoliddispersionof tadalafil: Repurposing with improvedtherapy in pyelonephritis. Asian J. Pharm
2017;
Sci.
12 (6):569-579.
- SD
SCANNING ELECTRON MICROSCOPY (SEM)
✓ TDL SMEC-SD revealed smooth, homogenous and uniform films with no evidence of Cur crystallization.
✓ TDL SD revealed crystals of with cracks on the film.
33 TDL SMEC-SD TDL
PHARMACOKINETIC STUDY
KIDNEY HISTOPATHOLOGY
TDL SMEC SD No Kidney toxicity
BIOMARKER ESTIMATION
BLOOD UREA NITROGEN (BUN)
NITRIC OXIDE (NO2)
SERUM CREATININE (SCR)
TDL SMEC SD
2
BUN SCR NO
CONCLUSION
• PRESENTS PLATFORM TECHNOLOGY AND AFFORDABLE EXCELLENCE
•
ATGSDF PRESENTS SIMPLE AND ELEGANT COMBINATION OF SOLID DISPERSION, SMEDDS AND FILM TECHNOLOGIES AS A NEW AND ADVANCEDSTRATEGY FOR BIOENHANCEMENT
37
INSTITUTE OF CHEMICAL TECHNOLOGY MUMBAI
PVD RESEARCH GROUP
HUGE THANKS TO ALL MY STUDENTS OVER THE YEARS
SPDS
ACKNOWLEDGEMENTS
SPDS US CHAPTER
RESEARCH STUDENTS
•
•
• MY
40 THANK YOU