dissolution method intended for pharmaceutical dosage forms comprising coated beads within hard gelatin or HPMC capsules. It ensures reproducible drug release profiling, detection of burst release or incomplete release, and meets regulatory expectations for modified-release formulations.

2. Scope

This procedure applies to all dissolution method development activities conducted by the Analytical Method Development department for multiparticulate capsule dosage forms containing coated beads, particularly in controlled-release and delayed-release formulations.

3. Responsibilities

• Analytical Scientist: Designs and executes dissolution studies, selects apparatus, and analyzes release profiles.
• Formulation Scientist: Provides composition, coating details, and bead characteristics (e.g., size, coating thickness).
• QA Reviewer: Reviews and approves method development protocols and validation reports.
• Instrumentation Officer: Maintains dissolution test apparatus and ensures calibration.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring that the developed dissolution method is discriminatory, robust, and aligned with ICH, USP, and FDA guidelines, and is suitable for quality control and stability studies.

5. Procedure

5.1 Pre-Development Considerations

1. Collect information on:
   • Bead core composition and API solubility
   • Coating type (enteric, sustained release, barrier)
   • Desired release profile (immediate, delayed, or sustained)
2. Refer to reference listed drug (RLD) or pharmacopeial monograph, if applicable.

5.2 Apparatus and Medium Selection

1. Choose appropriate dissolution apparatus:
   • USP Apparatus I (Basket): Recommended if beads float
   • USP Apparatus II (Paddle): Suitable with sinkers or gel caps
2. Select medium based on:
   • API solubility (use surfactants like SLS for poorly soluble drugs)
   • Simulated gastric or intestinal conditions (pH 1.2, 4.5, 6.8)
   • Use of buffer and enzymes where required (e.g., pancreatin for enteric coatings)

5.3 Sample Preparation and Dosing

1. Use 6 or 12 capsules (1 per vessel) as per standard protocol.
2. If needed, embed capsule in sinker or use capsule holding device to avoid flotation.
3. Ensure bead uniformity by inspecting for fill weight and visible defects before testing.

5.4 Sampling Strategy

1. Define sampling time points based on intended release profile:
   • Immediate Release: 5, 10, 15, 20, 30 min
   • Modified Release: 1, 2, 4, 6, 8, 12 hr
   • Enteric Coated: Acid stage: 0.5–2 hrs, Buffer stage: 15, 30, 60 min post pH shift
2. Use automated or manual sampling; replace volume with fresh medium maintained at 37°C ± 0.5°C.

5.5 Analytical Method and Detection

1. Analyze samples using HPLC or UV, depending on specificity and API stability.
2. For multi-component beads (e.g., dual drug systems), develop individual quantitation methods.
3. Ensure filter compatibility studies are performed for dissolution samples (see Annexure-3).

5.6 Data Interpretation and Profile Evaluation

1. Calculate cumulative % drug release using absorbance/peak area data and standard calibration curve.
2. Assess profile shape (e.g., zero order, first order, Higuchi, Korsmeyer-Peppas).
3. Evaluate variability across vessels (%RSD ≤ 10% at each time point for IR, ≤ 20% for MR).

5.7 Method Validation

1. Validate the method for:
   • Specificity: Placebo interference check
   • Linearity: 5–7 levels across expected range
   • Precision and intermediate precision: At multiple time points
   • Accuracy: Spike recovery studies in dissolution medium
   • Robustness: Agitation speed ± 5 rpm, pH variation ± 0.2 units

6. Abbreviations

• HPLC: High-Performance Liquid Chromatography
• USP: United States Pharmacopeia
• MR: Modified Release
• IR: Immediate Release
• RSD: Relative Standard Deviation

7. Documents

1. Dissolution Method Development Protocol – Annexure-1
2. Method Validation Report – Annexure-2
3. Filter Compatibility Evaluation – Annexure-3

8. References

• USP <711> Dissolution
• FDA Dissolution Testing Guidance for Immediate Release Solid Oral Dosage Forms
• ICH Q2(R1): Validation of Analytical Procedures
• WHO Technical Report Series No. 992 Annex 7

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Anjali Saxena	Mehul Sharma	Dr. Harshita Goyal
Designation	Analytical Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	Quality Assurance	Analytical Method Development

11. Annexures

Annexure-1: Dissolution Method Development Protocol

Includes: product details, dose strength, API characteristics, coating description, method intent, medium selection rationale, apparatus, RPM, sampling points, and expected outcome.

Annexure-2: Method Validation Summary

Parameter	Result	Criteria	Status
Linearity (R²)	0.9989	≥ 0.999	Pass
Recovery (Accuracy)	99.2% – 101.5%	98–102%	Pass
Precision (RSD)	2.1%	≤ 5%	Pass

Annexure-3: Filter Compatibility Evaluation

Filter Type	Recovery (%)	Observation	Accepted
0.45 µm Nylon	99.8	Clear, no retention	Yes
0.45 µm PVDF	96.4	Adsorption observed	No

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/06/2025	2.0	Added validation requirements and filter compatibility	Annual Review	Dr. Harshita Goyal
12/05/2022	1.0	Initial Release	New SOP	QA Head