Slide 1: HEMANT VINEETH BIOPHARMACEUTICS
PRESENTED BY: WHAT IS MEANT BY “DISSOLUTION” ?. : WHAT IS MEANT BY “DISSOLUTION” ?. A process in which a solid substance is solubilised in a given solvent that is mass transfer from solid surface to liquid phase .
It is a process by which drug released from solid dosage form and immediately goes into molecular solution . Why do we study dissolution ? : Why do we study dissolution ? Dissolution Absorption Drug in blood and body fluids deaggregation Theories on dissolution : : Theories on dissolution : Diffusion layer model or film theory.
danckwert’s model or surface renewal theory.
Interfacial barrier model. Diffusion layer model : : Diffusion layer model : 1.Simplest and most common .
2.Absence of reactive/chemical forces dissolution involues two steps
i.formation of stragnated film/diffusion layer .
ii.diffusion-slower,rate determining step.
Noyes and whitney equation:
Dc/dt=DAKw/o(cs-cb)/vh Danckwert’s model: : Danckwert’s model: 1. Did not approve existence of stragnated layer.
2. Turblance in dissolution medium exists at solid- liquid interface.
3. Pocket of eddys current absorb the solute by diffusion.
Vdc/dt=dm/dt=A(cs-cb).√¥D Interfacial barrier model: : Interfacial barrier model: 1.Assumption of previous models.
2.Intermediate conc. exist at the interface as a result of solvation mechanism it is function of solubility rather than diffusion. Factors affecting & processes influenced by Dissolution: : Factors affecting & processes influenced by Dissolution: TEMPERATURE PH STATE OF DRUG ABSORPTION DISSOLUTION BIOAVAILABILITY Slide 9: DISINTEGRATION DISSOLUTION PERMEATION BODY FLUIDS ABSORPTION SOLUBILITY RDS FOR ABSORPTION DISSOLUTION RDS FOR ABSORPTION : SOLUBILITY RDS FOR ABSORPTION DISSOLUTION RDS FOR ABSORPTION ? 1.CISAPRIDE-low solubility , high dissolutionlow dosage . 2.salt form of drugs –in bulk solution form fine particles. ↓ low soluble , high dissolution because of high effective surface area 3. aspirin –more soluble ,more hydrolytic stability so less base absorption. : 1.CISAPRIDE-low solubility , high dissolutionlow dosage . 2.salt form of drugs –in bulk solution form fine particles. ↓ low soluble , high dissolution because of high effective surface area 3. aspirin –more soluble ,more hydrolytic stability so less base absorption. Goals of predictive dissolution test: : Goals of predictive dissolution test: To accessing therapeutic efficacy.
Monitoring batch to batch consistency .
High cost of in vitro dissolution test.
Assessment of bioequivalence. Based on presence of sink or non sink conditions dissolution apparatus are classified as : : Based on presence of sink or non sink conditions dissolution apparatus are classified as : 1.Closed compartment apparatus
2.Open compartment apparatus TYPES OF DISSOLUTION APPARATUS : USP dissolution apparatus (official):
1. Apparatus 1:Basket type
2. Apparatus 2:Paddle type
3. Apparatus 3:Reciprocating cylinder
4. Apparatus 4:Flow through cell
5. Apparatus 5:Paddle over disc
6. Apparatus 6:Rotating cylinder
7. Apparatus 7:Reciprocating disc
USP dissolution apparatus (non-official):
Rotating bottle method.
Intrinsic dissolution method. TYPES OF DISSOLUTION APPARATUS IP dissolution apparatus :Apparatus 1:Paddle typeApparatus 2:Basket type : IP dissolution apparatus :Apparatus 1:Paddle typeApparatus 2:Basket type BP dissolution apparatus :
Apparatus 1:basket type
Apparatus 2:paddle type
Apparatus 3:flow through cell USP Apparatus 1 :Basket type Design:a)Vessel :-Made up of borosilicate glass -Semi hemispherical bottom -Capacity 1000ml b)Shaft : -Stainless steel 316 -Rotates smoothly without significance wooble c)Basket :- Stainless steel 316 -Gold coatings up to 0.0001 inch d)Waterbath : Maintained at 37±0.5⁰c : USP Apparatus 1 :Basket type Design:a)Vessel :-Made up of borosilicate glass -Semi hemispherical bottom -Capacity 1000ml b)Shaft : -Stainless steel 316 -Rotates smoothly without significance wooble c)Basket :- Stainless steel 316 -Gold coatings up to 0.0001 inch d)Waterbath : Maintained at 37±0.5⁰c Use: Capsules,tablets,delayed release,
suppositories,floating dosage forms APPARATUS 2:PADDLE TYPE: : APPARATUS 2:PADDLE TYPE: Design:
2.Shaft:The blade passes through shaft so that bottom of blade fuses with bottom of shaft .
3.Stirring elements :- Made of tefflon
-For laboratory purpose
-Stainless steel 316
4.Waterbath :Maintain at 37±0.5⁰c
5.Sinkers:Platinum wire used to prevent capsule /tablet from floating Slide 19: Paddle type: APPARATUS 3 :RECEPROCATING CYLINDER : APPARATUS 3 :RECEPROCATING CYLINDER Design:
1.Vessel:Cylindrical flat bottom glass vessel
2.Agitation type: -Reciprocating
-Generally 5-35 rpm
3.Volume of dissolution fluids :200-250 ml
4.Water bath: Maintain at 37±0.5⁰c
Use : Extended release APPARATUS 4:FLOW THROUGH CELL : APPARATUS 4:FLOW THROUGH CELL Design:
1.Reservoir:For dissolution medium
2.Pump:-Forces dissolution medium through cell -holding a sample
-Flow rate 10-100 ml/min
-Laminar flow is maintained
-peristalic/centrifugal pumps are not recommended
3.Water bath: Maintain at 37±0.5⁰c
Major advantage : -to maintain sink conditions
-Large volume dissolution media is used. APPARATUS 5:PADDLE OVER DISK : APPARATUS 5:PADDLE OVER DISK Design
4.Sample holder : -Disk assembly that hold the product in such a way that release surface is parallel with paddle.
-Paddle is directly attached over disk assembly .
-Samples are drawn away b/w the surface of medium and top of paddle blade.
6.Temperature:32 ⁰c Slide 25: Paddle over disk apparatus Text Here APPARATUS 6:ROTATING CYLINDER : APPARATUS 6:ROTATING CYLINDER Design:
1.Vessel:In place of basket cylinder is used.
2.Cylinder:Stainless steel 316.
3.Sample:-Mounted to cuprophan (inner porous cellulosic material) an entire system is adhere to cylinder.
-Dosage unit is place in cylinder
and released from outside
4.waterbath: Maintain at 32±0.5⁰c
Use : transdermal patches cannot be cut
into small size. Slide 27: 2 APPARATUS 7:RECIPROCATING DISK : APPARATUS 7:RECIPROCATING DISK 1.Vessel:-Flat bottom cylindrical vessel
-Volume of dissolution medium 50-200ml
3.Sample:Placed on disk shaped holders.
-Reciprocating frequency 30 cycles/min.
5.Waterbath: Maintain at 32±0.5⁰c
Use : transdermal patches References: : References: United states pharmacopeia
Pharmaceutical dissolution testing –jennifer dressman,jennifer kramer Trust yourself : Trust yourself Guided by: lecturers
Deepthi Slide 32: Thank You