It is estimated that 70% to 80%1 of small molecule drug candidates in development today can be classified as poorly water-soluble. Since poorly soluble drugs are difficult to formulate as tablets, formulation scientists are opting for two-piece, liquid-filled, hard-shell capsules as a solution.
Liquid-filled, hard-shell capsules (LFHCs) were introduced in the early 1980s, as an alternative to softgels. Drugs ideally suited for liquid-filled capsules are those with poor water solubility and bioavailability, with low melting points, potent drugs, hot liquids, and where a sustained-release drug profile is desirable.
In addition to being a great solution for formulating compounds with poor solubility, LFHCs can be rapidly developed and tested—so you can move your product quickly from R&D to the clinic. Different dosages can be manufactured on the same specifications by adjusting the amount of active ingredient and, when it’s time to go to market, the scale-up of the manufacturing process for commercialization is straightforward.
Their advantages include ease of scalability and manufacturing, ease of packaging, and high product stability. They also offer abuse-deterrent benefits because they make it harder to insufflate, inject, or alter the extended-release properties of potent drugs. Most importantly, unlike softgels, hard-shell gelatin capsules offer the possibility of combination filling. Drugs can be encapsulated in the form of beads, micro tablets, and pellets, in combination with the liquid formulation. This way, you can incorporate multiple previously incompatible drugs in a single capsule, in a formulation that is effective, stable, and esthetically pleasing to consumers.
LFHCs also offer a great opportunity for line extensions, and brand differentiation, in the competitive pharma market. They are an ideal option for reintroducing existing products in a new format to revitalize the brand, or if you are looking to reformulate for faster onset of action, gain better efficacy, or combine two existing active pharmaceutical ingredients (APIs) into a new drug product.
They also provide a versatile solution for the safe and effective handling and delivery of highly potent active pharmaceutical ingredients (HPAPIs) and other complex APIs which require controlled handling during manufacture to minimize risk to operators.
Benefits of a hard-shell exterior
A liquid drug formulation filled in hard gelatin capsule requires excipients, such as lipophilic liquid or semisolid vehicles, solubilizing agents, surfactants, and emulsifying agents. When it comes to formulation development and manufacturing, LFHCs provide numerous benefits over other solid oral dosage forms, such as:
- use of excipients with higher melting points when using HPMC capsules
- improved content uniformity of low-dose active and potent compounds
- enhanced stability
- lower moisture content
- less gas transmission
- improved bioavailability
A complete, simplified solution
The benefits of LFHCs can be summarized by what we, at Altasciences, call the 5 S’s―Speed, Savings, Solubility, Safety, Scalability. With this highly marketable dosage form, scientists can effectively formulate poorly soluble drugs and supplements, while reducing development time and costs.
As an integrated CRO/CDMO, Altasciences can quickly determine if your API has the attributes to benefit from a LFHC dosage form, and safely get your drug to market faster.
Contact our experts today to discuss your drug development and manufacturing needs.