At Teva api R&D, we work extremely closely with our customers to develop drug substances that best fit their formulation needs.
In generic API development, we identify the most likely formulation and focus on potential critical attributes in the API that may impact the formulation process and properties. When providing CDMO services, our focus is to develop APIs to make the formulation process development easier and increase probability of success in clinical trials.
Our aim is to offer the customer APIs which will be the most suitable to formulate, based on dosage form. We offer:
- Several crystalline forms (when possible).
- Several API grades,tailored to accommodate customers’ needs
- An extensive API characterization package with special focus on formulation-relevant attributes, including PSD, particles morphology, SSA, BD, and TD.
Once we gain an understanding of a customer’s potential dosage form and specific formulation, API attributes are tailored based on the identified needs of the pharma team, taking into account bioavailability and stability requirements, manufacturability, and IP limitations. Each route of administration, dosage form and formulation, has a specific focus regarding API development.
Oral dosage forms
An oral solid dosage form (OSD) includes tablets, suspensions and capsules. Tablets are the most common type of OSD, about one third of all prescriptions. In fact, sources estimate OSD to be approximately 65% of the market.
Most oral drug products are categorized by the Biopharmaceutics Classification System, the BCS, as part of the innovator’s NDA filing.
BCS is tool used for classifying orally administered medicines based on dissolution, aqueous solubility and intestinal permeability, which affect the absorption of active pharmaceutical ingredients (API).
Our teams take the BCS classification into account when selecting the crystalline form of the API for development. Many molecules being approved have low solubility, or BCS class II or IV, so require special attention.
Whether it is a crystalline anhydrous form, a solvate, or a salt, the API attributes are finetuned to match the formulator needs.
Nowadays, more and more API products have low solubility, therefore require special attention from the formulator and from us. The crystallization process has paramount importance to define the crystalline form (or to afford amorphous API), but also to finetune particle size and morphology, in combination with the particle size reduction technique that may be applied.
Another challenging case is when there is high loading of the API within the drug product, that in specific products might reach above 25% weight per volume (w/v) in a capsule. Extra care about API properties must be taken when developing for such high loading formulations.
API properties have a major impact on the formulation process and attributes of the drug product.
Physical-chemical properties of an API, including flow ability, mechanical properties and chargeability, will all be taken into consideration by our teams through all stages of development, depending on the specific formulation.
Bulk properties of API particles will be specially tailored to facilitate formulation development and to enable robust formulation process.
APIs for inhalation products
Another example of drugs strongly impacted by API characteristics are inhalation products. Since the final drug product is administered in a device, such as an inhaler, the quality of the API is often very low.
Examples of this are dry powder inhalers or metered dose inhalers. Here, the API is formulated mainly with lactose or gas. API attributes are of special importance here since the number of components is very limited – just the API, usually one or two additional excipients and the device itself. Each component has a massive impact on the efficacy of the product, unlike other drugs where there is a lengthier list of excipients.
The drug also needs to reach a specific place in the lung, which is dependent on particle size. If the size of the particle is too big, they will be deposited in the mouth or throat. If the API particle is too small, it will not readily sediment and could be exhaled.
As an API developer, we can leverage the ability to change morphology and PSD according to the customer’s choice of device. Critical attributes such as amorphous content and SSA will be carefully monitored in any particle size reduction treatment.
Since the optimal physical characteristics of the API will depend on the device, all API properties must be tailored to the specific needs of the customer. This includes particle morphology, PSD, surface characterization, amorphous traces, flow ability, density, chargeability, and mechanical properties.
Suspensions
Lastly, suspensions are used in various administrations either for injections, for topical administration such as creams, or for oral administration. Each type of suspension needs special consideration as the formulation may be liquid or semisolid, oily, aqueous.
Developing a suspension requires special attention to the surface properties of the API particles, which are in direct interaction with the continuous phase in formulation from which absorption takes place and therefore therapeutic effect.
In all these cases the thermodynamic balance which will enable stable suspension formulation requires that surface properties of a crystalline or amorphous API, base salt or a co-crystal API will be custom-made and fully characterized.
Nowadays, with CDMOs increasingly leading innovation for pharmaceutical partners, we are required to go the extra mile to speedily develop high-quality APIs and accommodate the specific needs of the customer.
We therefore implement cutting edge computational modeling, automation and high-throughput screening (HTS) in our development. Customers can also rely on the support of the Teva api team to holistically support their specific needs either in generic or specialty drug product development.
For more information on our CDMO services or APIs, please reach out to our team.
