Drug developers face a variety of challenges with formulation complexity for many of today’s drug products. Chief among them are solubility and bioavailability challenges of APIs. Excipients play an important role in overcoming these challenges.

Lubrizol offers an array of pharmaceutical excipients for oral, topical and injectable applications. The company’s portfolio of specialty materials is designed to provide application-specific solutions to simplify the drug development process, enhance drug delivery, stability, and efficacy.

The formulation benefits of Lubrizol’s excipients Apisolex, Apinovex, and Carbopol allow for more patient-centric therapeutic regimens with smaller dosages or reduced dosage frequency. These products can also help to improve manufacturing processes by supporting leaner processing, minimizing production complexity and waste, and accelerating timelines.

Liliana Miinea, Global Technology Manager, Lubrizol Pharmaceuticals R&D shares insight on the challenges drug developers face and solutions for today’s complex drug products.

Contract Pharma: What are some common formulation challenges drug developers face with today’s drug products?

Liliana Miinea: Up to 90% of new chemical entities and over 40% of those in reformulation have poor aqueous solubility, presenting formidable challenges to drug developers. These “brick-dust” APIs are typically BCS Class II, with high permeability but poor solubility, or Class IV, which are poorly permeable and poorly soluble. As a result, they’re difficult to disperse in water-based formulations, leading to poor bioavailability. These characteristics increase formulation complexity and heighten the risk that a promising drug will not reach the market.

Contract Pharma: What role do excipients play in overcoming these challenges?

Liliana: Formulators can employ a range of excipient-based technologies to address solubility and bioavailability challenges of APIs. 

Amorphous solid dispersions (ASDs), for example, increase dissolution by disrupting the API’s crystalline structure and maintaining it in an amorphous state. Polymer encapsulation integrates APIs into polymer carriers, while micelles sequester poorly soluble APIs within a hydrophobic core, surrounded by a hydrophilic shell, enabling dispersal in aqueous environments. 

The choice of excipients can also impact patient compliance. This is increasingly important as regulators place greater emphasis on improving the patient experience to encourage adherence to treatment.

Contract Pharma: What are some examples of drug products that could benefit from Lubrizol’s excipients? 

Liliana: Lubrizol’s Apisolex™ polymer excipient is a novel polyamino acid-based amphiphilic excipient designed to dissolve and stabilize hydrophobic APIs for intravenous infusion and bolus injection. Based on sarcosine –a non-toxic, non-immunogenic, biocompatible, and biodegradable amino acid – it offers a high level of safety for parenteral use. Demonstrated to increase drug solubility by up to 50,000 times, Apisolex™ polymer excipient achieves drug loadings of up to 40%. This can enable more patient-centric therapeutic regimens with smaller dosages or reduced dosage frequency.

For oral solid dosage products, Lubrizol’s Apinovex™ polymer is a novel, high molecular weight linear polyacrylic acid excipient. Developed for use with ASDs, it allows more efficient dosage forms with high, stable drug loading of up to 80% – twice that of other commonly used solubility-enhancing excipients. This enables more efficient and patient-centric oral solid therapeutics, including smaller, easier-to-swallow tablets.

Where extended-release profiles are required in oral solid dosage forms, Carbopol® polymers are highly efficient gel matrix formers for controlling drug release in solid dosage forms. The polymers have demonstrated slower drug release rates at lower concentrations than other commercially available excipients (such as cellulosics), enabling overall formulation cost savings and smaller tablet sizes. Lubrizol’s Carbopol^® polymer excipients have a crosslinked structure, providing longer controlled drug release at lower inclusion levels. Carbopol^® polymers work alone or in synergy with cellulosics such as hydroxypropyl methylcellulose (HPMC) to extend API release rate, enabling lower levels of matrix former polymers in the formulation and smaller tablet sizes.

Contract Pharma: How can these products help to improve manufacturing processes?

Liliana: Lean manufacturing is increasingly important as the pharmaceutical industry reevaluates its environmental impact and sustainability strategies. Novel excipients such as Lubrizol’s Apisolex™ and Apinovex™ polymers can support leaner processing, accelerating time to market while minimizing production complexity and waste. Apisolex™ polymer, for example, facilitates simple formulation techniques such as solution mixing or oil-in-water emulsification before sterile filtration and lyophilization, and with greater than 90% API recovery. Soluble in water and commonly used pharmaceutical solvents, including isopropanol and ethanol, Apinovex™ polymer produces low-viscosity solutions for easier processing by solvent evaporation techniques.

For oral solid therapeutics, Carbopol^® polymers enable highly efficient gel matrix formation, at low polymer usage levels. Granulation – where fine, non-compactible powders are transformed into coarser agglomerates that can be compressed into tablets – adds complexity and cost to the manufacturing process. Using Carbopol^® 71G NF polymer, which is directly compressible, removes the granulation step, helping manufacturers reduce the time and expense of these processes, while minimizing material waste.

Contract Pharma: What advances are being made with excipient and ingredient technology and what can we expect in the near term with respect to novel drug products, dosage forms, and or drug delivery?

Liliana: Many excipients with precedence of use are suboptimal for transforming today’s difficult-to-deliver APIs into marketable drugs. In this context, early collaboration between manufacturers and excipient suppliers is essential for building formulator confidence in novel excipients.

At Lubrizol, we work closely with formulators to co-develop data and prepare regulatory submissions. Our patent-protected, novel polymer excipients enable IP protection not offered by traditional excipients. Additionally, they facilitate reformulation of existing APIs, enabling developers to extend the life cycle of established drugs or pursue accelerated approval pathways such as the FDA’s 505(b)(2).

Learn more here: www.lubrizol.com