# Optimization design of solution preparation methods of three poorly soluble drugs of clinical use in infusions on orthogonal test and evaluation of stability study

## TL;DR

This study finds the best ways to prepare three hard-to-dissolve antibiotics for IV use and confirms they stay stable for 24 hours.

## Contribution

Optimized preparation methods and stability data for three poorly soluble intravenous antibiotics using orthogonal testing.

## Key findings

- Oxacillin sodium dissolves best in 8mL of 0.9% NS with 90s shaking.
- Cefmetazole sodium dissolves best in 8mL of 5% GS with 120s shaking.
- Ciprofloxacin hydrochloride dissolves best in 18mL of 5% GS with 120s shaking and remains stable for 24 hours.

## Abstract

To optimize the preparation methods of three intravenous poorly soluble antibacterial drugs (oxacillin sodium, cefmetazole sodium, and ciprofloxacin hydrochloride) and investigate their compatibility and stability in infusion.

Taking the variety of solvents, volume of initial solvent, and oscillation time as influencing factors, and with the count of particulate matter and content uniformity in the preparation solution as the evaluation indices, the L9(34) orthogonal test was used to optimize the preparation methods of three intravenous insoluble antibacterial drugs. Simulate clinical drug concentrations, mix each drug separately with 0.9 % sodium chloride (0.9 % NS) and 5 % glucose (5 % GS), and take samples at different time points under room temperature and refrigerator conditions to determine their appearance, pH value, and relative percentage of drug content.

The optimal preparation method for oxacillin sodium was as follows: it was pre-dissolved in 8 mL of 0.9 % NS and shaken for 90 s before dilution and preparation. The optimal preparation method for cefmetazole sodium was as follows: it was pre-dissolved in 8 mL of 5 % GS, and shaken for 120 s before dilution and preparation. The optimal preparation method for ciprofloxacin hydrochloride was as follows: it was pre-dissolved in 18 mL of 5 % GS, and oscillation for 120 s before dilution and preparation. The three drugs were combined with 0.9 % NS and 5 % GS, respectively, and remained relatively stable within 24 h.

Optimal selection of the variety of solvents, the volume of the initial solvent, and the oscillation time in preparing poorly soluble antibiotics can improve the quality of the intravenous infusion. Stability experiments confirmed that the three drugs can remain stable for 24 h, ensuring safety during clinical intravenous infusion.

Image 1

•Inadequate dissolution of insoluble injections may cause particles and dosing inaccuracy.•Orthogonal test optimized IV formulation for three insoluble antimicrobial drugs.•Compound stability study clarifies storage conditions for formulated drugs.

Inadequate dissolution of insoluble injections may cause particles and dosing inaccuracy.

Orthogonal test optimized IV formulation for three insoluble antimicrobial drugs.

Compound stability study clarifies storage conditions for formulated drugs.