Seminar On

In vitro dissolution testing models

Presented byMr. Prashant Gaikwad

Under Guidance ofDr. A Srinatha

• The Usp-NF provides several official methods for

carrying out dissolution test.

• The selection of a particular method for a drug is

usually in the monograph for a particular drug product.

Apparatus Name Drug product

Apparatus 1 Rotating basket Tablets

Apparatus 2 Paddle Tablets, capsules, suspension

Apparatus 3 Reciprocating cylinder

Extended release

Apparatus 4 Flow cell Low water soluble drug

Apparatus 5 Paddle over disk Transdermal

Apparatus 6 Cylinder Transdermal

Apparatus 7 Reciprocating disk Extended release

Rotating bottle Non-USP-NF Extended release (beads)

Diffusion cell (Franz)

Non-USP-NF Ointments, creams, Transdermal

Based on the absence or presence of sink conditions dissolution apparatus are 3 types

1. Closed-compartment apparatus

2. Open- compartment apparatus

3. Dialysis apparatus

Factors must be considered in design of dissolution tests:1. Factors relating the dissolution apparatus

2. Factors relating to the dissolution fluid

3. Process parameter e.g. method of introducing dosage form, sampling techniques, changing dissolution fluid etc.

Apparatus 1 (Rotating basket)

The assembly consist

1. A covered vessel

• Cylindrical, hemispherical bottom

• Diameter is 98-106 mm & normal capacity 1000 ml

2. Motor, metallic drive shaft

• Fabricated of stainless steel type

3. Cylindrical basket

• Gold coating 0.0001 inch (2.5 µm)

Apparatus 2 (Paddle)

•The assembly is same as apparatus 1 except that a paddle formed from a blade & a shaft is used as stirring element.

•The metallic blade & shaft comprise a single entity that may be coated with a suitable inert coating.

Apparatus 3 (reciprocating cylinder)

The assembly consist:1.Set of cylindrical, flat bottomed glass vessels2.Set of reciprocating cylinders3.Stainless steel fittings (type 316 or equivalent)4.Polyproylene screens5.Motor & drive assembly

Apparatus 4 (Flow through cell)• The assembly consist of

– Reservoir & pump for dissolution medium– A flow through cell– A water bath

•The flow through cell is transparent & inert mounted vertically with filters.•Standard cell diameters are 12 & 22.6 mm. •The bottom cone usually filled with glass beads of 1 mm diameter.•Tablet holder used for positioning special dosage form e.g. inlay tablets.

Cell Types

Tablets 12 mm Tablets 22.6 mm Powders / Granules Implants Suppositories / Soft gelatin capsules

Flow-Through Apparatus

Apparatus 5 (Paddle over disk)•The assembly consist-Cylindrical vessel-Motor drive shaft-Paddle-Stainless steel disk

•Disk- minimize “dead volume” between disk assembly & bottom of vessel

•Disk- holds the system flat & release surface parallel with the bottom of paddle blade.

Apparatus 6 (Reciprocating cylinder)

• Use assembly from

apparatus 1

• Replace basket with

stainless steel cylinder

• Dosage unit placed on the

cylinder

Apparatus 7 (Reciprocating disk)• This apparatus consist

– Containers

– Set of disk shaped sample

holder

– Motor & drive assembly

• Reciprocate at frequency of

about 30 cycles/min.

Rotating Bottle

• Used for controlled release beads

• Consist a rotating racks that holds sample in bottles

• Bottles are capped tightly & rotated in 37ºC water

bath.

• At various time, samples are collected from bottle,

decanted from 40 mesh screen & residues are

assayed.

Diffusion cells• Used for topical &

transdermal drug products.

• Franz diffusion cell is static diffusion system used for characterizing drug permeation through skin model.

• The source of skin may be cadaver or animal skin.

Interpretation• The amount of drug dissolved within a given time period (Q)

is expressed as a percentage label content.Acceptance Table:

Stage Number tested

Acceptance criteria

S1 6 Each unit is NLT Q +5 %

S2 6 Average of 12 units (S1+S2) is equal to or greater than Q, & no unit less than Q - 15%

S3 12 Average of 24 units (S1+S2+S3) is equal to or greater than Q, NMT 2 units are less than Q- 15% & no unit is less than Q- 25%

References• The United States Pharmacopeia, NF-18, Asian Edition, 1995,

Page no. 1791-1799

• Leon Shargel, Applied Biopharmaceutics & Pharmacokinetics,

5th Edition, 2005, Page no. 424-430

• Brahmankar & Jaiswal,Biopharmaceutics & Pharmacokinetics

A Treatise, Vallabh Prakashan, Page no. 291

• http://www.labplus.co.kr/tech/tech_note.asp?not_no=270

• http://www.pharmacopeia.cn/v29240/usp29nf24s0_c711h.html

• http://apps.who.int/phint/en/d/Jb/7.5.6.html

• http://www.pharmacopeia.cn/v29240/usp29nf24s0_c724h_viewall.html