💊 Drug Dissolution Test
Testing of active substance release from tablets and capsules under in vitro conditions using USP apparatus (basket, paddle, flow-through cell). Key bioequivalence study.
Overview
The dissolution test is one of the most important pharmaceutical tests determining the rate and extent of active substance release from oral solid dosage forms (tablets, capsules, granules) under in vitro conditions. Chapter 2.9.3 of the European Pharmacopoeia (Ph. Eur.) defines apparatuses, test conditions and acceptance criteria.
The test is crucial in drug quality control — the dissolution profile correlates with in vivo bioavailability of the drug. In the drug registration process, the dissolution test is required to demonstrate bioequivalence of generic drugs with the original. In routine quality control it is performed for each production batch.
The Pharmacopoeia defines 4 main apparatuses: Apparatus 1 (rotating basket), Apparatus 2 (paddle), Apparatus 3 (reciprocating cylinder) and Apparatus 4 (flow-through cell). Apparatuses 1 and 2 are most commonly used. The dissolution medium (usually 500–1000 mL of buffer at specified pH) is maintained at 37.0 ± 0.5°C, simulating gastrointestinal tract conditions.
Results from Ph. Eur. 2.9.3, USP <711> and JP 6.10 are mutually recognized in ICH regions, facilitating global drug registration. The test is internationally harmonized by ICH Q4B Annex 7.
Method principle
A tablet or capsule is placed in a vessel with dissolution medium at controlled temperature (37°C) and agitated at specified speed (basket or paddle). At specified time intervals, medium samples are taken, filtered and the active substance concentration is determined by spectrophotometric (UV-Vis) or chromatographic (HPLC) method. The result is expressed as percentage of released drug dose as a function of time. For single-stage test, min. 6 vessels (dosage units) are required.
Applications
- Quality control of tablets and capsules in each production batch
- Bioequivalence studies of generic drugs (comparison with reference)
- Formulation development — optimization of composition and manufacturing process
- Stability studies — changes in dissolution profile over time
- Comparison of dissolution profiles (f1/f2 similarity factor)
- Dissolution test of modified-release tablets (extended-release)
Key parameters
| Parameter | Value |
|---|---|
| Medium temperature | 37.0 ± 0.5°C |
| Medium volume | 500–1000 mL (most commonly 900 mL) |
| Stirring speed | 50–100 rpm (paddle), 100 rpm (basket) |
| Number of vessels | 6 (S1), 12 (S2), 24 (S3) — acceptance stages |
| Acceptance criterion (S1) | Each of 6 units ≥ Q + 5% at specified time |
| Dissolution media | pH 1.2 (HCl), pH 4.5 (acetate), pH 6.8 (phosphate), water |
Standard
- Standard number
- Ph. Eur. 2.9.3 (Farmakopea Europejska, 11. wydanie)
- Title (PL)
- Test rozpuszczalności stałych postaci leku
- Title (EN)
- Dissolution test for solid dosage forms
Step-by-step procedure
1. Medium preparation
Prepare dissolution medium according to drug monograph (pH 1.2 / 4.5 / 6.8 or other). Degas under vacuum or ultrasonication.
2. Vessel filling
Fill 6 vessels with measured volume of medium (usually 900 mL). Place in apparatus and heat to 37.0°C.
3. Temperature verification
Verify medium temperature in each vessel with calibrated thermometer. Tolerance ±0.5°C.
4. Sample introduction
Place one tablet/capsule in each vessel. For apparatus 1 — in basket. For apparatus 2 — directly into vessel (sinker if form floats).
5. Start stirring
Start rotation at specified speed (e.g. 50 rpm paddle). Simultaneously start stopwatch.
6. Sample collection
At specified times (e.g. 5, 10, 15, 30, 45, 60 min) collect medium samples (5–10 mL) from each vessel. Filter through 0.45 µm.
7. Medium replenishment
Replenish the collected volume with fresh medium at 37°C (or apply volume correction in calculations).
8. Concentration determination
Measure sample absorbance (UV-Vis) or perform HPLC analysis. Calculate concentration from calibration curve.
9. Calculation of % release
Calculate percentage of released dose: % = (C × V × 100) / (declared dose). Include corrections for collected volume.
10. Results assessment
Compare results with acceptance criterion (S1: each ≥ Q+5%). If not met — proceed to S2 (6+6) or S3 (6+6+12).
Required equipment and apparatus
| Equipment | Example | Indicative price |
|---|---|---|
| Dissolution apparatus | Agilent 708-DS, SOTAX AT Xtend, ERWEKA DT 820, Distek Evolution 6300 | 80 000–250 000 PLN |
| Water bath / thermostat | Integrated with apparatus, stability ±0.5°C | Included |
| UV-Vis spectrophotometer | Agilent Cary 60, Shimadzu UV-1900i, Thermo Evolution 201 | 25 000–80 000 PLN |
| HPLC (alternatively) | Agilent 1260 Infinity II, Waters Alliance e2695, Shimadzu Nexera | 150 000–350 000 PLN |
| Syringe filters | PVDF/PTFE 0.45 µm, 25 mm, Millipore, Whatman | 200–500 PLN / 100 pcs |
| Dissolution vessels | Glass vessels 1000 mL with lids, according to USP specification | 300–800 PLN / pc |
Reagents, media and consumables
| Reagent | CAS | Details |
|---|---|---|
| Hydrochloric acid 0.1 mol/L (pH 1.2) | 7647-01-0 | Medium simulating gastric juice, without enzymes |
| Acetate buffer pH 4.5 | 64-19-7 | Acetic acid + sodium acetate, according to Ph. Eur. |
| Phosphate buffer pH 6.8 | 7558-80-7 | Simulation of small intestine conditions, KH₂PO₄ + NaOH |
| Polysorbate 80 (Tween 80) | 9005-65-6 | Surfactant added to medium for poorly soluble substances (0.1–2%) |
| Reference substance | — | Active substance standard of known purity for preparation of calibration curve |
| Purified water | — | According to Ph. Eur. (conductivity ≤ 4.3 µS/cm at 20°C), as medium or solvent |
Health and safety (OHS)
- Hydrochloric acid 0.1 mol/L — corrosive substance, use gloves and protective glasses
- Temperature 37°C — risk of burns when medium is spilled
- Glass vessels — caution during handling (filled vessel mass ~1 kg)
- Work with active substances — use appropriate protection (lab coat, gloves)
- Degassing under vacuum — do not exceed vacuum vessel parameters