We offer comprehensive amorphous solid dispersion (ASD) services, using small quantities of material, in order to help customers improve the solubility and bioavailability of pharmaceutical compounds.

  • Increase the apparent solubility of the API and maximize bioavailability
  • Accelerate drug development by helping to select the right drug candidate at an early stage
  • Provide an alternative approach to enhancing bioavailability
  • Maximize the chances of creating a successful new drug product
  • Understand and maximize dissolution behavior to help predict in vivo behavior
  • Generate IP
  • Extend the life of a product or patent and help develop new generations of a drug

Performing amorphous solid dispersion studies, in parallel with our other solid state services, enables effective candidate selection at an early stage, increasing the chances of successful development.

Improving Bioavailability

For a large proportion of APIs in development, bioavailability is limited by poor aqueous solubility.
Creating an amorphous solid dispersion is one way to improve bioavailability and increase the effectiveness of a drug. In order to stabilize an amorphous form, the API is combined with a polymer to produce a single-phase amorphous mixture of the API and the polymer.

 

Enhanced Dissolution Profile

By using an amorphous phase in a solid dosage form, you can take advantage of the higher apparent solubility of the amorphous relative to that of a crystalline form to achieve high levels
of supersaturation in aqueous media. Polymers and excipients used in the ASD formulation can aid stabilization of the supersaturated state after dissolution of the API.

 

A diagram to show the dissolution rates of different solid forms

 

Polymer Selection

Selecting the right polymer is essential to ensure the resultant amorphous solid dispersion delivers the drug properties you require. It is important to consider the following when selecting the right polymer:

  • Regulatory approval for the required route of administration
  • The maximum polymer loading that can be used (a smaller polymer loading is desirable to reduce pill burden)
  • The properties of the API, such as thermal stability or solubility
  • The desired properties of the amorphous solid dispersion, such as increased solubility, dissolution rate, controlled release, and stabilization of saturated solution
  • The required stability of final product

Polymers may be selected to give a targeted drug release. Drugs for immediate release may be soluble in gastric fluid but others may require some degree of gastro-resistance, dissolving at a specific pH to target a defined area of the intestine.

Screening

Screening can be used to help identify the best polymers to use to form a stable amorphous solid dispersion with a particular API. We will choose the most appropriate screening method for a particular API. The method chosen will depend on the API properties including thermal stability and solubility in organic solvents.

 

ASD chart

 

Amorphous Solid Dispersion by Spray Drying

Spray drying is widely used in the manufacture of amorphous solid dispersions due to its fast-drying rate. During spray drying, it is possible to manipulate the processing parameters to change the particle properties in a single step process.

 

Diagram of a spray dryer

Diagram to show the components of a spray dryer

 

Watch our video: Introducing Spray Drying at Veranova

Amorphous Solid Dispersion by Coprecipitation

Direct formation of ASDs using coprecipitation can be carried out using common equipment that is readily available in drug substance manufacturing facilities.

 

Characterization Studies

Veranova is well positioned to develop new amorphous dispersions quickly. Through small scale screening and evaluation of properties, we can identify suitable candidate systems and
scale them up to 10s of grams.

Veranova can perform a number of analytical characterization services including:

  • X-ray powder diffraction (XRPD) to determine whether the material is amorphous
  • Modulated temperature differential scanning calorimetry (MDSC) to understand the stability of the amorphous phase
  • Thermogravimetric analysis (TGA) to assess thermal characteristics and volatile content
  • Dissolution analysis using Sirius Inform to ensure the ASD has sufficient performance

Case Studies

Enhancing the dissolution rate of a BCS Class 2 drug

Problem

A number of different solid form and particle engineering techniques were investigated at Veranova with the aim of enhancing the dissolution rate of a BCS Class 2 drug. A dissolution method was required to compare their effectiveness.

Scope of work carried out by Veranova

  • Preparation of spray dried ASD of the API with PVP/VA (30% loading of piroxicam) using Buchi B290 lab scale spray dryer
  • Preparation of known ethanolamine mono-salt and succinic acid hemi-cocrystal of the API using literature methods
  • Small scale dissolution method developed ( 6.5 mg free form equivalence), designed to compare the initial dissolution rate of the different engineered particles
  • Maximum concentration of 0.25 mg/mL of the free form in 1 % (w/v) Tween 80 and 1 % (w/v) HPMC in SGF at 37 °C

Outcome

The micronised sample showed the highest initial dissolution rate within the first two minutes at 0.56 mg/min.

Total release after 30 min was highest for the ASD.

Increasing the initial dissolution rate of a BCS Class 2 API using ASD

Problem

Increase the initial dissolution rate of a BCS Class 2 API using an amorphous solid dispersion (ASD). Generate and investigate the dissolution rate of the ASDs compared to the crystalline API to select the best candidate(s) for further development.

Scope of work carried out at Veranova

  • ASD samples were generated by spray drying on a 2-5 g scale using a Buchi B290 lab scale spray dryer.
  • Three different polymers, HPMCAS, Plasdone S630 and Soluplus were investigated with three different drug loadings, 20% DL, 30% DL and 50% DL.
  • The dissolution performance of the samples was analysed using the Sirius inForm instrument in sink conditions.
  • Disc method: ASDs were pressed into 6 mm disc and immersed into the media at 37 °C, in PBS buffer at pH 7.4, 40 mL of buffer, with UV spectra collected every 30 s for 30 mins. About ~45 mg of sample were used per disc.
  • Free powder method: The powder was added manually over the media at 37 °C in PBS buffer, pH 7.4, 40 mL of media, UV spectra collected every 30 s for 60 mins. Sufficient ASD was weighed to account for drug loading to be under sink conditions.

Outcome

  • Plasdone S630 ASDs had the fastest dissolution rate, followed by HPMCAS, then Soluplus both from disc and free powder assays
  • The time to release 75 % of the API was improved with Plasdone S630 and HPMCAS more or almost two-fold compared to crystalline Piroxicam. Soluplus showed a slower release time.

Overall, the Plasdone S630 ASDs with a high 50% drug loading can be recommended on the basis that it is the optimal formulation for a fast dissolution and low excipient mass.

Solid Form Sciences

Amorphous Solid Dispersion

Chiral Resolution and Confirmation

Crystallization development

Enabling Formulation

Particle Size Modification

Physicochemical & Solid Form Profiling

Salt, Cocrystal & Polymorph Screening

Structure Confirmation

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