Super Refined™ pharmaceutical excipients – by Croda

Looking to enhance the bioavailability, delivery and efficacy of your dosage form? With Croda’s highly purified functional excipients, you can optimise the stability of your API and the overall performance of your pharmaceutical formulations. Our catalogue contains a range of products that exceed the stringent requirements of the pharmaceutical industry, being compliant with all the latest Ph. Eur., USP/NF, JP/JPE, and ChP monographs. Croda also aims to constantly increase the number of ChP-compliant excipients.

Croda’s ongoing commitment to high quality standards and investment in R&T ensures the continual delivery of exceptional high purity ingredients and the development of new speciality products to answer the current and future needs of the pharmaceutical industry.

Croda’s Super Refined range:

• Oils and esters
• Polysorbates
• Poloxamers
• PEGs
• Lanolins
• Propylene glycol

Super Refined excipients

The high level of purity afforded by Croda’s proprietary Super Refining process helps to maintain the chemical profile of your Active Pharmaceutical Ingredient (API), reducing the chance of oxidation and thereby helping to extend its shelf life. Super Refining removes polar and oxidative impurities from a vast range of excipients while retaining the fundamental structure and without affecting the monograph compliance.

Super Refined oils and esters

Our Super Refined naturally derived triglyceride oils and esters offer the highest and most consistent quality, often exceeding pharmacopoeia specifications. They also have excellent organoleptic properties, as they are essentially colourless, odourless and tasteless.

The stability of haloperidol decanoate in Super Refined Sesame Oil and standard compendial grade equivalents was investigated, to determine the effect of excipient purity on API degradation. In Super Refined Sesame Oil more than 93% haloperidol decanoate recovery was obtained after incubation at 40ºC for 12 weeks. In contrast, the recovery rate in standard compendial excipients varied between 68% and 79%, showing enhanced stability of the API in Super Refined Sesame Oil in comparison with standard compendial grade alternatives. These results demonstrate that the purity levels provided by the Super Refining process offer the formulator improved API stability and consequently improved performance.

API stability is enhanced in Super Refined excipients compared to standard compendial grade products

Super Refined PEGs

PEGs are some of the most commonly used excipients and are exceptionally good solubilisers for polar APIs. However, the impurities found in standard PEGs present a number of challenges when formulating with oxidatively unstable APIs. The presence of these impurities can accelerate the degradation of the API as well as destabilising emulsions, causing skin and cellular irritation and promoting gelatin crosslinking in both soft gelatin and hard gelatin capsules.

Optimise the stability of your API with Croda’s range of Super Refined excipients

Through our Super Refining process, we eliminate many of the impurities that are normally present in pharmaceutical grade polyethylene glycols, such as moisture, residual catalyst, peroxide and aldehydes.

In both Super Refined and standard compendial grade PEGs there is a reduction in recovery of fulvestrant after 12 weeks at 40°C. This is accompanied by the presence of an additional peak in the chromatogram (Figure 2). 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 appears 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. The removal of polar impurities helps to reduce API interaction, maintaining the stability of both the drug and the finished formulation.

Super Refined Polysorbates

Another frequently used group of excipients are polysorbates, which are hydrophilic, non-ionic surfactants widely used as emulsifying agents in the preparation of stable oil-inwater pharmaceutical emulsions. They are also excellent solubilisers, stabilisers, wetting and dispersing agents. However, like many other standard pharmaceutical grade excipients they contain impurities that cause formulation challenges, especially when working with oxidatively unstable APIs. To resolve these issues Croda provides a range of Super Refined polysorbates.

The data presented in Figure 3 shows docetaxel recovery in polysorbate 80 over a 12-week period at 40ºC. In Super Refined Polysorbate 80, the recovery rate after 12 weeks was greater than 90%. In contrast, the recovery of docetaxel in polysorbate 80 from three other sources dropped to between 20% and 60% after 4 weeks and between 10% and 50% after 12 weeks.

Super Refined Polysorbate 80 POA is a ChP-compliant grade developed specifically to meet the needs of the global market

Super Refined Poloxamer 188

Super Refined™ Poloxamer 188 is added to mammalian cell culture media to protect cells from shear stress caused by agitation in a bioreactor. Super Refined™ Poloxamer 188 has been optimised specifically for mammalian cell culture with tightly controlled impurity profiles and molecular weight, ensuring optimal cell culture performance and batch-to-batch consistency. As a product belonging to our Super Refined™ range, Super Refined™ Poloxamer 188 meets excellent purity standards, undergoes rigorous quality testing, is offered in enhanced packaging, and is also suitable for use as a parenteral excipient in biologic formulations.

Super Refined Propylene Glycol

Propylene glycol can be used in a range of pharmaceutical applications as a solvent, stabilising agent, water-miscible co-solvent, humectant, plasticiser and anti-microbial preservative. Unfortunately, propylene glycol tends to oxidise readily to form propionaldehyde, lactic acid, pyruvic acid and acetic aldehyde. To remove impurities which can accelerate the excipient’s oxidation Croda processes the excipient via its proprietary Super Refining technology. This provides propylene glycol of the highest purity, specifically for formulations containing sensitive active ingredients, where purity is paramount.

Our high purity Lanolins

Emollients soothe, smooth and hydrate the skin. They are of great therapeutic value in the treatment of a number of dermatological disorders. With an evolutionary advantage over other topical excipients, Medilan is uniquely engineered to imitate the natural lipids of the skin. By replenishing these essential lipids, Medilan is able to accelerate the repair of the skin’s natural barrier function, whilst simultaneously protecting against microbial infection.

Croda’s Medilan range includes three lanolin products processed via Croda’s Super Refining technology: Medilan Ultra, Medilan Super and Liquid Medilan Ultra. These products offer exceptional purity, beyond that of monograph compliance. These pure and hypoallergenic products deliver outstanding efficacy in dermatological applications, as well as proven safety in use.

Super Refined Brij O2

This highly purified Oleth-2 is a co-emulsifier liquid with suspended solids that is ideal for use in topical and auricular applications. Super Refined is a polyoxyethylene vegetablebased fatty ether derived from oleyl alcohol. This naturally derived, mild, and virtually odourless non-ionic surfactant can contribute spreading and stabilising properties to emulsions. It can be utilised as a high purity solubiliser or in emulsifier systems where a low HLB value is required.

Empowering biologics delivery

See the full technical brochure on Super Refined™ pharmaceutical excipients here

(click the picture to download the brochure)

Source: Croda, technical brochure Super Refined™ pharmaceutical excipients

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