You are hereAN OVERVIEW OF APPROACHES IN DISSOLUTION TESTING: A REVIEW

AN OVERVIEW OF APPROACHES IN DISSOLUTION TESTING: A REVIEW


About Authors:
Prashant L. Pingale, Anjali P. Pingale  
Department of Pharmaceutics & Quality Assurance,
School of Pharmacy and Technology Management, NMIMS Shirpur Campus
Shirpur Dist: Dhule Maharashtra
INDIA 425405.

ABSTRACT:
Tablets or capsules taken orally remain one of the most effective means of treatment available. The effectiveness of such dosage forms relies on the drug dissolving in the fluids of the gastrointestinal tract prior to absorption into the systemic circulation. The rate of dissolution of the tablet or capsule is therefore crucial.
Drug release in the human body can be measured ‘in-vivo’ by measuring the plasma or urine concentrations in the subject concerned. However, there are certain obvious impracticalities involved in employing such techniques on a routine basis. These difficulties have led to the introduction of official ‘in-vitro’ tests which are now rigorously and comprehensively defined in the respective Pharmacopoeia.
Although initially developed for oral dosage forms, the role of the dissolution test has now been extended to ‘drug release’ studies on various other forms such as topical and transdermal systems and suppositories.

Reference Id: PHARMATUTOR-ART-1173

Introduction:
Dissolution testing is an official test used by pharmacopeias for evaluating drug release of solid and semisolid dosage forms.[1]
In 1962 dissolved drug, known to be necessary for physiologic action which became an increasingly demand for its recognition that capsule and tablet monographs in which the drug substance had the solubility of less than 1 in aqueous media should be include in dissolution requirements.[2]

According to the guideline mentioned in B.P., it is expected that all new monographs for conventional-release capsules and tablets shouldcontain a dissolution requirement except  (i) where the solubility of the active ingredient is 10% or better in water, in dilute hydrochloric acid, at approximately 20° (ii) where the nature or intended use of the preparation renders a dissolution test inappropriate (for example, liquid-containing capsules, dispersible, effervescent, chewable or soluble tablets) and(iii) in other justified and authorized circumstances.

Dissolution tests were first developed to quantify the amount and extent of drug release from various dosage forms like[1, 3, 4]

*         Powders,
*         A floating microsphere,
*         Immediate release tablets,
*         Dosage forms for the oral cavity,
     (i)  Chewable tablets,
     (ii) Buccal /sublingual tablets,
     (iii) Medicated chewing gum,
*         Extended-release tablets,
*         Transdermal patches,
*         Soft gelatin capsules,
*         Suppositories,
*         Semisolid dosage forms,
*         Aerosol,
*         Nutritional supplements,
*         Suspension,
*         Pulmonary dosage form

When the concentration of dissolved drug (C) is less than 20% of the saturated concentration Cs, the system is said to operate under sink condition. The driving force for dissolution is greaterwhen the system is under sink conditions. [2]

Various Dissolution Apparatus according to USP and BP. [4, 5]

1) Apparatus 1 (Basket Apparatus) A dosage unit is placed in a dry basket at the beginning of each test.

2) Apparatus 2 (Paddle Apparatus) The assembly from apparatus 1 is used, except that a paddle is formed from a blade and a shaft is used as the stirring element.

3) Apparatus 3 (Reciprocating Cylinder):It consists of flat-bottomed glass vessel and a set of glass reciprocating cylinders. A device is used allows the reciprocation rate to be selected and maintained at specified dip rate given in the individual monograph within ±5%. [11]

4)Apparatus 4 (Flow-Through Cell)[9] The assembly consists of a reservoir and a pump for the dissolution medium; a flow-through cell; and a water bath that maintains the dissolution medium at 37 ± 0.5oC.
Use the specified cell size as given in the individual monograph. The pump forces the Dissolution Medium upwards through the flow-through cell.
It must deliver a constant flow (±5% of the nominal flow rate); the flow profile is sinusoidal with a pulsation of 120 ± 10 pulses per minute.

5) Apparatus 5 (Paddle over disk)
Same as apparatus 2 but stainless steel disk is fitted in the bottom for holding transdermal dosage form.

6) Apparatus 6 (Cylinder)
The vessel assembly used is same as apparatus 1, except the basket and shaft is replaced with a stainless steel cylinder on which dosage form is kept.

7) Apparatus 7 (Reciprocating Cylinder)

Note –Apparatus 1 and 2 according to IP is Paddle Apparatus and Rotating basket apparatus respectively.

Table 1. Details of construction of Paddle type apparatus

Characteristic

USP

BP

IP

Vessel height           

160-210mm

160mm

168 ± 8m

Paddle shaft diameter(before coating)

9.4-10.1mm

9.4-10.1mm

9.75 ± 0.35mm

Blade upper chord

74.5-75.0mm

74.5-75.0mm

74.5-75.0mm

Blade lower chord

42 ± 0.1mm

42.0mm

42.0mm

Height

19.0 ± 0.5mm

19.0 ± 0.5mm

19.0mm

Radius disk

41.5 ± 1mm

41.5mm

41.5mm

Thickness of blade

4.0 ± 1mm

4.0 ± 1mm

4.1 ± 1mm

Device distance from bottom

25± 2mm

25± 2mm

25 ± 2mm

Table 2. Details of construction of Basket Apparatus

Characteristic

USP

BP

IP

Basket shaft

6.3-6.5 or     9.4-10.1 mm

6.3-6.5 or   9.4-10.1 mm

9.7 ± 0.3 or

6.4 ± 0.1 mm

Basket material (stainless steel)

Type 316

Type 316

Type 316

Vent hole

2.0 ± 0.5 mm

2.0± 0.5 mm

2.0 mm

Retention Spring

3 tangs

3 tangs

3 tangs

Clear opening

20.2 ± 0.1 mm

20.2 ± 1.0 mm

22.2 ± 1.0 mm

Wire diameter

0.25 mm

0.25-0.33mm

0.254mm

RPM

25-150

100

100

Height of screen

27.0 ± 1.0mm

27.0 ± 1.0mm

27.0 ± 1.0mm

Total height of basket

36.8 ± 3.0mm

37.0 ± 3.0mm

36.8 ± 3.0mm

Height of upper cap

5.1 ± 0.5mm

5.1 ± 0.5mm

5.1 ± 0.5mm

Total height of basket

37.0 ± 3.0mm

37.0 ± 3.0mm

36.8 ± 3.0mm

Table 3. Various dosage forms and type of apparatus used for

Sr. No.

 

Dissolution test of Dosage Form

Type of apparatus used

(according to USP   and BP) [5,6]

1

Immediate release dosage form

1, 2, 3*, 4

2

Extended release dosage form

1, 2, 3*, 4

3

Delayed  release dosage form

1, 2, 3*, 4

*Not accepted by the Japanese Pharmacopoeia (JP)

Table 4. Reciprocating cylinder

Characteristic

USP

BP

Glass vessel height(mm)

180 ± 1

180 ± 1

Glass vessel diameter(mm)

47 ± 1.4

47 ± 1.4

Glass reciprocating tube length(mm)

100 ± 1

100 ± 1

Glass reciprocating tube diameter(mm)

23-26

23-26

Tube Air hole diameter(mm)

3.9 ± 0.1

3.9 ± 0.1

Evaporation cap height (mm)

66.8 ± 1

66.8 ± 1

Evaporation cap diameter(mm)

50.8 ± 1

50.8 ± 1

Cap Air hole

3.9 ± 1

3.9 ± 1

Table 5. Flow through cell

Characteristic

USP

BP

Sieve 40 mesh diameter

0.2

0.2

Internal diameter

20 ± 0.2

20 ± 0.2

Outer  diameter

22.5 ± 0.2

22.5 ± 0.2

Angle

40 ± 1o

40 ± 1o

Tablet holder height

6.5 mm

6.5 mm

Tablet holder thickness

0.5 mm

0.5 mm

Tablet holder width

7.5 mm

7.5 mm

 

Table 6. Comparison of common specification of various dissolution apparatus [4, 5, 6]

Characteristic

USP

IP

BP

JP

Dissolution vessel         

 

Nominal capacity

1 L – 4 L

Nominal capacity 1 L

Nominal capacity 1 L

Nominal capacity 1 L

Shaft position

 

NMT 2mm from vertical axis

NMT 2mm from vertical axis

NMT 2mm from vertical axis

NMT 2mm from vertical axis

Allowable variation in                    (RPM)

±4%.

 

±4%.

 

±4%.

 

±4%.

 

Shaft rotation speed

50-100

50-100

50-150

---

Distance of bottom of apparatus to inside bottom of apparatus.

25 ± 2 mm

 

25 ± 2 mm

 

25 ± 2   mm

 

25 ± 2 mm

 

Apparatus suitability test

Specified

Not specified

Not Specified

Not specified

Temperature maintained

37 ± 0.5

 

37 ± 0.5

 

37 ± 0.5

 

37 ± 0.5

 

*JP = Japanese Pharmacopoeia

APPARATUS SUITABILITY [5, 6]
The determination of suitability of a test assembly isto perform dissolution testing which includes the conformance of dimensions and tolerances of the apparatus as given above.
In addition, critical test parameters that have to be monitored periodically during use include volume and temperature of the Dissolution Medium, rotation speed (Apparatus 1 and Apparatus 2), and dip rate (Apparatus 3), and flow rate of medium (Apparatus 4).
Determine the acceptable performance of the dissolution test assembly periodically. The suitability for the individual apparatus is demonstrated by the Apparatus Suitability Test.

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT articles@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE


FIND MORE ARTICLES

Subscribe to RSS headline updates from:
Powered by FeedBurner