Stability of APIs in Super Refined PEG - Maximise the Performance of Your Active Pharmaceutical Ingredients

Discover the Benefits of Super Refined Excipients

Polyethylene glycols (PEGs) are excipients that are widely used in oral, parenteral and topical delivery dosage forms. Low molecular weight PEGs, such as PEG 300 and PEG 400 in particular, are used as solvents in concentrated formulations that are then diluted prior to injection via infusion.

As PEGs can be used at relatively high concentration in the formulation, it is important that they do not cause the Active Pharmaceutical Ingredient (API) to degrade.

A screening study on the stability of APIs in standard compendial excipients has revealed that 5 out of 10 APIs are unstable in PEG 400.

Croda’s range of Super Refined™ excipients has been specially developed to optimise API stability and improve performance of pharmaceutical formulations. Super Refined materials demonstrate clear benefits, adding real value to the drug development process.

Benefits of Super Refined Excipients

Enhanced API and formulation stability
Fewer formulation degradation products
Minimised analytical complexity
Simplified formulations
Reduced resource, time and development costs
Improved chance of formulation success
Multi-compendial – NF, PhEur, JPE

The following case studies demonstrate the effect of excipient purity on the stability of two APIs, fulvestrant and diltiazem hydrochloride.

Case Study: Fulvestrant Stability in PEG 400

Fulvestrant (Figure 1) is a selective oestrogen receptor degrader, used to treat hormone receptor positive metastatic breast cancer in post-menopausal women. It is a steroid with an alkyl-sulfinyl moiety, delivered via intramuscular injection in a formulation that contains castor oil.

Stability of APIs in Super Refined PEG_Figure 1 Structure of fulvestrant — Figure 1 Structure of fulvestrant

API recovery

The results for fulvestrant at 40°C in PEG 400 are shown
in Figure 2. In standard compendial grade PEG 400 the API recovery rate after 12 weeks was 34%. In contrast, the recovery rate in Super Refined PEG 400 was considerably higher at 74%. This demonstrates that the stability of fulvestrant in Super Refined PEG 400 is substantially higher than in the corresponding standard compendial grade.

Stability of APIs in Super Refined PEG_Figure 2

API degradation

In both Super Refined and standard compendial grade excipients the reduction in recovery is accompanied by the presence of an additional peak in the chromatogram (Figure 3). Fulvestrant elutes at a retention time of 5.1 minutes. An additional peak also elutes at a retention time of 6.9 minutes. Even though this peak is appearing in both grades of PEG 400, the height is considerably lower in the Super Refined PEG 400. This demonstrates the substantially increased stability of the API in Super Refined PEG 400.

Stability of APIs in Super Refined PEG_Figure 3

Key Findings

The stability of fulvestrant is substantially enhanced in Super Refined PEG 400 in comparison with that in standard compendial grade PEG 400
Formulation in Super Refined PEG 400 results in substantially less degradation than is seen in a standard compendial grade product

Case Study: Diltiazem Hydrochloride Stability in PEG 400

Diltiazem hydrochloride (Figure 4) is a calcium channel blocker, used in the treatment of angina and hypertension. It is a nondihydropyridine class of calcium channel blocker based on benzothiazepine. It is usually administered orally as a tablet or capsule. It has also been administered via injection and topical cream.

Stability of APIs in Super Refined PEG_Figure 4 Structure of diltiazem hydrochloride — Figure 4 Structure of diltiazem hydrochloride

See the full brochure “Maximise the Performance of Your Active Pharmaceutical Ingredients” by Croda´s Stability of APIs in Super Refined PEG here

(click the picture to download the brochure)

Source: Croda brochure “Maximise the Performance of Your Active Pharmaceutical Ingredients”

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