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 ± 0.5^oC.
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

Table 2. Details of construction of Basket Apparatus

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

^*Not accepted by the Japanese Pharmacopoeia (JP)

Table 4. Reciprocating cylinder

Table 5. Flow through cell

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

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.

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Apparatus Suitability Test ^[4]
Apparatus 1 and 2— individually test 1 tablet of the USP Dissolution Calibrator, Disintegrating Type and 1 tablet of USP Dissolution Calibrator, Non disintegrating Type, according to the operating conditions specified.
The apparatus is suitable if the results obtained are within the acceptable range stated in the certificate for that calibrator in the apparatus tested.
Apparatus 3— individually test 1 tablet of the USP Drug Release Tablets (Single Unit) according to the operating conditions specified. The apparatus is suitable if the results obtained are within the acceptable range stated in the certificate.
Apparatus 4 – It is yet to come.

Conventional-release dosage forms ^{[3, 5, 6, 7]}
Conventional-release dosage forms are preparations showing a release of the active substance(s) which is not deliberately modified by a special formulation design and/or manufacturing method. Equivalent term: immediate-release dosage form.

Modified-release dosage forms
Modified-release dosage forms are preparations where the rate and/or place of release of the active substance(s) are different from that of a conventional-release dosage form administered by the same route. This deliberate modification is achieved by a special formulation design and/or manufacturing method. Modified-release dosage forms include prolonged-release, delayed-release and pulsatile-release dosage forms.

Prolonged-release dosage forms
Prolonged-release dosage forms are modified-release dosage forms showing a slower release of the active substance(s) than that of a conventional-release dosage form administered by the same route. Prolonged-release is achieved by a special formulation sdesign and/or manufacturing method. Equivalent term: extended-release dosage form.

Delayed-release dosage forms
Delayed-release dosage forms are modified-release dosage forms showing a release of the active substance(s) which are delayed.
Delayed release is achieved by a special formulation design and/or manufacturing method. Delayed-release dosage forms include gastro-resistant preparations as defined in the general monographs on solid oral dosage forms.

Pulsatile-release dosage forms
Pulsatile-release dosage forms are modified-release dosage forms showing a sequential release of the active substance(s). Sequential release is achieved by a special formulation design and/or manufacturing method.

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