Please tell me about BASF in general and the products and services it offers the pharmaceutical industry?
BASF creates chemistry for a sustainable future offering intelligent solutions to the pharmaceutical industry. With our expertise in polymer chemistry, R&D-capabilities and our commitment in developing excipients, BASF continuously creates solutions for Instant & Modified Release, Solubilization, Softgels, Skin-Delivery and Biologic Solutions. BASF is also the leading supplier of selected APIs such as ibuprofen and omega-3.
Hot melt extrusion (HME) has been around for a while and has been used in other industries. What does this technology offer pharmaceutical manufacturers and how can they incorporate it into their current drug development processes?
Hot melt extrusion is a unique process which offers the great capability of dispersing APIs into matrices. Polymeric matrices are a great example of overcoming the high crystal lattice energy of actives, one of the root causes for their poor solubility. The resulting solid dispersions are a formulation type in which the drug is already dissolved (moleculary dispersed) and in fact the polymer controls dominantly the drug release rate. Most of the existing and newly developed actives have issues with the available oral bioavailability. Often a too high melting point (high crystal lattice energy) and/or their pronounced hydrophobicity are the reasons for insufficient bioavailability. By molecularly dispersing the drug with the help of the compounding process (intimately mixing inside the extruder), is a first step of improving the dissolution rate. Secondly, with the addition of surfactants, hydrophobic actives can be micellated after their release from the melt extruded solid dispersion to maintain them in supersaturated solution until they have been fully absorbed into the blood stream.
To implement hot melt extrusion in drug development processes companies typically pull people with different expertise together: engineers to design and optimize the extrusion and compounding process, formulators to design and understand the formulation approach of a solid dispersion. Both disciplines need to work and interact closely together as the success of the formulation development strongly depends on the expertise built in both engineering and formulation science area. BASF helps their customer with tailored inhouse events but also with other publications such as the hot-melt extrusion compendium to become faster and to avoid typical mistakes.
What HME products and services does BASF offer to the industry? What benefits do they provide your current and future customers?
The basic ingredients for a solid dispersions are:
Polymers. BASF offers a variety of functional polymers from povidone range, copovidone, methacrylates but also specifically for the HME process developed polymers such as Soluplus®.
Surfactants, which act as a wetting agent and solubilizer for drugs where the solubility limitation is not just the dissolution rate but the apparent solubility. Here BASF focuses on surfactants with higher HLB to micellate drugs in an aqueous environment. Prominent examples of solubilizers are Kolliphor® RH40 and Kolliphor® EL, but also different poloxamers.
Disintegrants, which are important to ensure a proper dispersion of the melt extruded solid dispersion after its being applied. Polymers typically can tend to dissolve slower than small molecules such as sugar. Important is to support the dissolution and disintegration with disintegrants, which are blended to the extra-granular phase. BASF offers different crosspovidones for this application such as Kollidon® CL.
BASF has a more than 35-year history and real experience in hot melt extruded solid dispersions. This knowledge and experience we share with our customers and thus enable a faster develop of their formulation. Our BASF experts are trained to understand the possibilities but also the limitations, that melt extruded solid dispersions offer. We help our customers with in-depth expertise level but also with an honest opinion. BASF’s support and service on concrete projects has been highly appreciated by our customers. Therefore, BASF will continue to help in technical formulation and process related questions as both topics are linked closely together. BASF’s service includes webinars, inhouse seminars, general face-to-face events or by publications of key topics in the industry.
Are there other technologies that complement HME? How does BASF leverage their pharmaceutical drug delivery expertise to incorporate HME, functional excipients and other technologies to help their clients meet their drug solubility and bioavailability goals?
There are complementary technologies to HME. Currently Spray Drying is the most versatile and industrial relevant. Moreover, many new technologies that have been developed or are currently under development, deal with the question of how to obtain a solid dispersion directly in a nano-particular structure such as nano-fibers or nanoparticles. Some of the technologies have been implemented already in the industry, i.e. electro-spinning. But it has to be stated that most of them are very niche applications. BASF critically evaluates whether a new technology addresses really unmet needs. The dialogue with our customers on the best drug delivery system / technology for the respective drug and the right choice of excipients play a key role in this evaluation. Besides solid dispersions, BASF’s expertise in solubilization also includes solutions in lipid-based drug delivery systems.
Looking toward the future, how will BASF continue to be a leader in functional excipients as it relates to HME and other drug delivery technologies?
BASF continues to be an innovative excipient supplier developing new excipients based on consolidated formulation trends. We are in close contact with our customers to understand their needs for any kind of excipient property. In cooperation with universities across the globe we support and evaluate new technologies and new formulations approaches. Our target is to develop value-adding solutions. With our solubilization platform we focus on questions around the solubility and ultimately the bioavailability enhancement of poorly bioavailable drugs.