ABISOL™ Emulsion Preconcentrate Kit

At ABITEC, we recognize that formulating self-emulsifying drug delivery systems is no easy task, and that developing unique emulsion formulations for every new molecule is not feasible.

Consequently, ABITEC has developed the ABISOL Emulsion Preconcentrate Kit: five unique emulsion preconcentrates with different hydrophobicity profiles. Finding the perfect nano-emulsion for your therapeutic is as simple as determining which ABISOL emulsion preconcentrate provides for the maximum solubility for the respective active.

 

ABISOL Emulsion Preconcentrate Kit Properties and Uses

Properties

ABISOL Emulsion Preconcentrates Properties

Calculated HLB’s of ABISOL Emulsion Preconcentrates

Hydrophobic-Lipophilic Balance (HLB) values for each preconcentrate are directly related to the excipient concentrations  in each blend. HLB values for each surfactant were determined by Griffin’s method. Using the surfactant HLBs and the required HLB (rHLB) for the oil, a total preconcentrate HLB was determined based on the weight percentage of the excipients utilized in each preconcentrate. Employing this method, five preconcentrates were created with HLBs spanning the scale between 5 and 10.

Physical Properties of ABISOL Emulsion Preconcentrates

ABISOL Emulsion Preconcentrates are uniform blends of four excipients; medium-chain triglycerides, mono- and di-glycerides, a low HLB surfactant, and a high HLB surfactant. The individual preconcentrates contain different weight percentages of the respective excipients. The physical properties of the individual preconcentrates are detailed in the table below.

Physical Properties I II III IV V
Appearance

Clear Amber

Liquid

Clear Amber

Liquid

Clear Amber

Liquid

Clear Amber

Liquid

Clear Amber

Liquid

Density @25°C (g/mL)

0.874 – 1.069

0.887 – 1.084

0.897 – 1.096

0.900 – 1.101

0.926 – 1.132

Viscosity @25° (cST)

79.4 – 97.0

101.2 – 123.6

143.2 – 175.0

185.0 – 226.8

261.3 – 319.3

Particle Size of ABISOL Emulsion Preconcentrates

ABITEC’s ABISOL Emulsion Preconcentrates are designed to spontaneously generate low globule size emulsions (< 150 nm) that have low polydispersity indices, when diluted in an aqueous environment. Small globule sizes allow for rapid dispersion and absorption in the gastro-intestinal tract, which is ideal for drug delivery. Each ABISOL Emulsion Preconcentrate exhibits a particle size less than 70 nm, when diluted in distilled water at a concentration of 1% (w/w) as demonstrated in the figure below.

Fig. Emulsions made with ABISOL preconcentrates.  Representative data composed of 1% w/w emulsions of each ABISOL preconcentrate prepared by adding 1 g of preconcentrate to 99 grams of deionized water and mixing for 5 minutes with a magnetic stir bar and magnetic stir plate.  Emulsion particle size and polydispersity indexes were obtained using a Malvern Zetasizer.

The preconcentrates maintain a similar globule size and polydispersity index  even upon dilution at different concentrations, as demonstrated with ABISOL Emulsion Preconcentrate I in the figure below.

Fig. Dilution series using ABISOL Emulsion Preconcentrate I. ABISOL Emulsion Preconcentrate I was diluted in water at various concentrations as noted in the image.  The globule size of each emulsion with each preconcentrate was measured and the intensity of each graph adjusted to the same scale for visualization purposes.

Regulatory

Uniform blends of the respective preconcentrates are formulated from different combinations of the following functional lipids: CAPTEX® 300 EP/NF, CAPMUL® MCM EP/NF, polyethoxylated castor oil EP/NF, and, at times, ACCONON® CMG-6 EP/NF at predefined w/w ratios. All excipients utilized are considered generally recognized as safe (GRAS) and meet monographs for U.S. Pharmacopeia and the National Formulary (USP-NF) and European Pharmacopoeia (EP).

 

Product Name USP-NF Description EP Description
CAPTEX 300 EP/NF Medium-Chain Triglycerides Medium-Chain Triglycerides
CAPMUL MCM EP/NF Glyceryl Mono and Dicaprylocaprate Glycerol Monocaprylocaprate Type I
ACCONON CMG-6 EP/NF Linoleoyl Polyoxylglycerides Linoleoyl Macrogolglycerides
Polyethoxylated Castor Oil Polyoxyl 35 Castor Oil Macrogolglycerol Ricinoleate

 

Application Data

As an example of the utility of the ABISOL Emulsion Preconcentrate Kit, a solubility case study was conducted with the model therapeutic Ibuprofen (IBU). IBU is a poorly soluble active under acidic conditions and is classified as a BCS II molecule with a Log P around 3.97.

Excess IBU was added to each preconcentrate, mixed by nutation for 24 hours at room temperature, and then the supernatant was clarified by centrifugation. The experiment was repeated in triplicate. The IBU concentration in each supernatant was measured and plotted in the graph below. Despite being highly hydrophobic, IBU had the highest solubility in ABISOL Emulsion Preconcentrate V which has a HLB value around 10. 

Figure . IBU solubility in ABISOL Emulsion Preconcentrates. Ibuprofen (1.6g) was added to 4 grams of each emulsion and briefly vortexed. The suspensions were placed in a sonicator bath for 30 minutes and then allowed to mix on a nutator overnight (24 hours) at room temperature. The suspensions were pelleted for 10 minutes at 3000 rpms and the supernatant (~1.5 mL) of each was transferred to a clean microcentrifuge tube. Each supernatant was centrifuged an additional 30 minutes at ~13,000 rpm. The supernatants were subsequently diluted 500-fold in ethanol and their absorbances read on a UV-Vis spectrophotometer at 265 nm. The obtained results were compared with the Ibuprofen standard curve to determine solubilities of Ibuprofen in each preconcentrate. Error bars represent an “n” value of 3

To better characterize the IBU + ABISOL Emulsion Preconcentrate V solution, a study measuring the globule size of each replicate was conducted. Here, the clarified supernatants of the IBU Solubility study conducted with ABISOL Emulsion Preconcentrate V were diluted to a 1% (w/w) emulsion with deionized water. The emulsions were then measured using a Malvern Zetasizer. The figure below displays the dynamic light scattering spectra of a representative scan. As demonstrated, the presence of IBU in the preconcentrate does increase the globule size as compared to the ABISOL Emulsion Preconcentrate V without IBU from ~20 nm to ~55 nm. However, as designed, the globule size remains below  150 nm.

 

FAQ

Q: Can I get a free sample of the ABISOL Emulsion Preconcentrate Kit?

A: Samples of the ABISOL Emulsion Preconcentrate Kit are not available.

 

Q: Can I purchase the kit using a credit card?

A: Currently ABITEC does not accept credit cards. ABITEC is working on adding credit cards as a payment option.

 

Q: How much is in each respective bottle of the ABISOL Emulsion Preconcentrates?

A: The ABISOL Emulsion Preconcentrate Kit comes with five different preconcentrates. Each bottle of preconcentrate contains 200 grams of the respective preconcentrate.

 

Q: Are there different pack sizes of the ABISOL Emulsion Preconcentrate Kit?

A: The ABISOL Emulsion Preconcentrate Kit comes in one size only.

 

Q: Can we modify the composition of the preconcentrates to suit our formulation needs?

A: Absolutely. The Emulsion Preconcentrates are intended to be a starting point for your formulation efforts.

 

Q: Will you provide the formulation percentages of each excipient?

A: ABITEC will share the formulation of a preconcentrate under an NDA, if a respective preconcentrate-active formulation  goes to clinical trials.

 

Q: Can we obtain a larger amount of just one of the preconcentrates?

A: ABITEC can provide cGMP lots of any blended preconcentrate at commercial scale volumes.

 

Q: Have you performed toxicology studies with the ABISOL Emulsion Preconcentrates?

A: ABITEC has used only GRAS excipients commonly found in marketed therapeutics to create these blends. All the excipients can be found in the inactive ingredient database, as a point of reference.

 

 

REQUEST QUOTE

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