during the preparation of the prototype formulations, ensuring that they meet quality specifications and are suitable for testing.

Project Managers: Coordinate the preparation and testing of prototype formulations, ensuring that timelines are met and resources are efficiently utilized.

4) Procedure

The following steps outline the procedure for preparing prototype formulations for testing:

1. Step 1: Define Formulation Requirements
   1. Identify the drug and therapeutic indication to ensure that the formulation meets the specific release and bioavailability requirements.
   2. Determine the desired drug release profile (e.g., immediate-release, controlled-release, extended-release) based on the drug’s pharmacokinetics and therapeutic needs.
   3. Establish the list of excipients to be used in the formulation, ensuring compatibility with the drug and its desired release characteristics (e.g., binders, diluents, lubricants, disintegrants, polymers for controlled release).
2. Step 2: Selection of Excipients
   1. Choose excipients based on their functionality (e.g., enhancing solubility, stability, or controlling release) and compatibility with the active pharmaceutical ingredient (API).
   2. Ensure that selected excipients do not cause degradation of the API, and consider excipient properties such as solubility, hygroscopicity, and ability to form a stable matrix for controlled release formulations.
   3. Perform compatibility testing, if necessary, to assess interactions between the API and excipients using techniques such as Differential Scanning Calorimetry (DSC) or Fourier-Transform Infrared Spectroscopy (FTIR).
3. Step 3: Formulation Preparation
   1. Prepare the prototype formulation by accurately weighing the API and excipients, following the formulation requirements defined in Step 1.
   2. Mix the ingredients using appropriate blending methods (e.g., dry mixing, wet granulation) to ensure uniform distribution of the drug and excipients.
   3. If preparing a tablet formulation, compress the formulation into tablets using a tablet press. Ensure that the tablets meet the required size, shape, and hardness specifications.
   4. If preparing capsules, fill the formulation into hard or soft gelatin capsules, ensuring proper filling weight and capsule integrity.
   5. If preparing oral solutions or suspensions, dissolve the API in a suitable solvent and add stabilizers, preservatives, or flavoring agents as needed to ensure stability and patient acceptability.
4. Step 4: Evaluation of Prototype Formulations
   1. Perform in-process testing during the preparation of prototype formulations to ensure uniformity, drug content, and consistency.
   2. Evaluate key parameters such as tablet hardness, friability, disintegration time, and dissolution rate for solid dosage forms.
   3. For liquid formulations, assess pH, viscosity, and drug concentration to ensure they are within the desired range.
   4. For controlled-release formulations, perform dissolution testing under USP conditions to evaluate the drug release profile.
5. Step 5: Stability Testing
   1. Conduct preliminary stability studies on the prototype formulations under accelerated conditions (e.g., 40°C, 75% RH) to evaluate potential degradation or changes in drug release characteristics over time.
   2. Monitor the physical and chemical stability of the formulations, including any signs of API degradation, changes in appearance, or alterations in dissolution profiles.
   3. Store the formulations under long-term conditions (e.g., 25°C, 60% RH) to assess their stability over time and compare the results with those from the accelerated studies.
6. Step 6: Data Collection and Analysis
   1. Record all experimental conditions, observations, and results during the preparation and evaluation of prototype formulations.
   2. Analyze the data to assess the performance of the formulations, including drug release rates, stability, and the impact of excipients on formulation performance.
   3. Identify any formulations that exhibit performance issues, such as poor drug release, instability, or undesirable physical properties, and adjust the formulation accordingly.
7. Step 7: Documentation and Reporting
   1. Document all findings, including formulation preparation details, testing results, and stability data, in a detailed report.
   2. Prepare a final report summarizing the formulation development process, including a description of the prototype formulation, its performance characteristics, and any recommended modifications for further development.
   3. Ensure that all records are signed, dated, and stored in compliance with Good Laboratory Practices (GLP) and regulatory standards.
8. Step 8: Sample Disposal
   1. Dispose of any remaining test samples, solvents, and testing materials according to safety protocols and environmental regulations.
   2. Ensure that hazardous materials, including excipients or solvents, are disposed of in designated chemical waste containers.

5) Documents

The following documents should be maintained during the preparation of prototype formulations:

1. Formulation Preparation Records
2. Compatibility Testing Reports
3. Stability Testing Records
4. Dissolution Testing Results
5. Data Analysis and Statistical Reports
6. Prototype Formulation Summary Report
7. Sample Disposal Records

6) Abbreviations

• API: Active Pharmaceutical Ingredient
• GLP: Good Laboratory Practices
• HPLC: High-Performance Liquid Chromatography
• USP: United States Pharmacopeia

7) References

References to regulatory guidelines and scientific literature that support this SOP:

• FDA Guidance for Pharmaceutical Development
• USP <1151> on Pharmaceutical Dosage Forms
• ICH Q8(R2) Pharmaceutical Development

8) Version

Version 1.0: Initial version of the SOP.

9) Annexure

Prototype Formulation Testing Results Template

Formulation ID	Drug Content (%)	Tablet Hardness (kg)	Friability (%)	Dissolution Profile	Stability Results