Post on 15-May-2018
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Improved Solubility
Improved Bioavailability
Improved Efficacy
Bottom-up particle assembly during
spray-drying process
Flowable, stable, instant powder.
Upon dispersion in aqueous media
forms nano-colloids
Depressed melting temperature and enthalpy of API
Improved dissolution and solubility in bio-relevant media
Less ordered-crystalline lattice
Submicron particles of API are
homogeneously dispersed in
polymer matrix
SolumerTM is composed of porous micro-
aggregates
Scientific Evidence Based Solumer Technology
SolumerTM is a Solubest proprietary, patent protected technology to produce stable and instant formulations of liphophilic compounds.
SolumerTM Introduction
Particle engineering during spray-drying process
Solubest’s proprietary technology implements spray-drying of API and polymer blend to produce submicron particles of API dispersed in a polymeric matrix. To achieve the optimum dispersion and smallest particle size, expertise based consideration is given to the composition of the feed solution and polymeric matrix.
Depressed melting point and enthalpy
Formulated API demonstrates significant reduction in melting temperature and enthalpy in comparison with raw crystalline material. Such high energy state requires less energy for dissolution!
SolumerTM: porous micro-aggregates
During the spray-drying process of API and polymer proprietary blend porous micro-aggregates of polymers embed the API nano-particles. The optimum result is achieved due to expertise based choice of the polymeric matrix composition.
Nano and Submicron particles of active compound are embedded in polymer matrix
Upon contact with water or biological fluids Solumer™ powder is self-dispersed to form uniform nano-colloids with mean particle size in a range of 0.5-5 µm. The colloidal particle is not entire monolith; it is built from subunits of 50-100 nm.
Less ordered-crystalline lattice:
Formulated API possesses a high energy crystalline structure, stabilized by interaction with polymers. Such disordered structure reduces the dissolution energy barrier, inherent in the typical rigid crystal of poorly soluble actives!
Improved dissolution and solubility
Formulated API exhibits significantly higher solubility in standard and biorelevant media in comparison with raw API and commercial drugs. Similarity in the saturation solubility of Solubest products in Fed and Fasted State Simulating Intestinal Fluids (FaSSIF& FeSSIF) can be translated to the decrease or complete eliminating of the drug food effect.
Powder characteristics
Flowability – easy handling and processing Compressability – allows multiple dosage forms Stability – long shelf life Bulk instant powder is easy to disperse in liquid
Solubility of native resveratrol and Solu-Resveratrol at 0.1% and 1% concentrations
SEM images demonstrate that SoluResveratrol is constructed from the porous polymer aggregates (100-200 µm) covered by submicron-micron particles of resveratrol (0.5-5 µm)
www.solubest.com/ +972-8-940-3023/ info@solubest.com
SolumerTM Essential Characteristics
200 nm
Freeze Fracture TEM image of SoluFenofibrate colloidal particle
Thermal X-Ray diffractograms demonstrate that SoluFenofibrate melts between 55oC and 65oC, while raw API stable at 70oC
Particle Size Distribution
0.01 0.1 1 10 100 1000 3000
Particle Size (µm)
0
2
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Volu
me (
%)
SoluGris-105-47+us2, 15:53:54 2010 ץרמ 08 ינש םוי
SoluGris-105-47+us2, 15:54:10 2010 ץרמ 08 ינש םוי
SoluGris-105-47+us2, 15:54:26 2010 ץרמ 08 ינש םוי
D10=421 nm D50=1027 nm
D90=5880 nm
SoluGriseofulvin particle size distribution measured by Laser Diffraction technique (Malvern instrument)
4.9300 mg
Integral -256.73 mJ normalized -52.08 Jg^-1Onset 44.35 °CPeak Height 7.02 mWPeak 49.20 °CExtrapol. Peak 49.92 °CEndset 53.42 °CPeak Width 5.60 °C
Integral -15.52 mJ normalized -3.15 Jg^-1Onset 56.88 °CPeak Height 0.44 mWPeak 63.57 °CExtrapol. Peak 63.91 °CEndset 66.90 °CPeak Width 5.84 °C
Integral -409.31 mJ normalized -81.86 Jg^-1Onset 80.09 °CPeak Height 23.71 mWPeak 81.74 °CExtrapol. Peak 81.73 °CEndset 84.80 °CPeak Width 2.77 °C
Method: DSC-30-100-10-N2-pan hermetically sealeddt 1.00 s 30.0-100.0°C 10.00°C/min, N2 80.0 ml/minSynchronization enabled
SF-PR-PD-19
5.000 mgFenofibrate
mW
10
°C30 35 40 45 50 55 60 65 70 75 80 85 90 95
^exo
--
16.05.2007 10:46:52
STARe SW 9.01
Lab: Ana
Melting of API in formulation
Melting of Raw Fenofibrate
Polymer Melting
Physical Mixture
80oC
55oC
DSC thermograms show that formulated fenofibrate possess depressed melting point in comparison with raw material or API in the physical mixture with polymers
5 10 15 20 25 30 35 40
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SoluTU-LG-114-126
Testosterone IndecanoateRM, Lot 110605
Inte
nsi
ty [
counts
]
2 Theta [deg]
Powder X-ray diffraction patterns of raw Testosterone ester and SoluBest Testosterone ester formulation. A broadening of the major formulated drug diffraction peak can be attributed to reduction of its effective crystallite size.
0
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0 20 40 60 80 100 120 140
% d
rug
dis
olv
er
Time (min)
Dissolution of SoluStatin NCE vs Raw API in FaSSIF and FeSSIF
Statin NCE in FaSSIF
SoluStatin NCE in FaSSIF
Statin NCE in FeSSIF
SoluStatin NCE in FeSSIF
API API CHARACTERISTICS FORMULATION CHARACTERISTICS
T melt (ºC) ΔH melt (J/g) T melt (ºC) ΔH melt (J/g) Particle size (nm)
Fenofibrate 81.5 74.3 64.4 9.3 669
Resveratrol 267.4 253.6 199.7 104.8 1190
Nifedipine 172.4 113.4 140.9 8.4 749
Itraconazole 169.7 84.4 155.6 21.9 910
Tacrolimus 135.0 60.5 118.0 52.0 836
Clarithromycin 227.6 70.2 207.9 40.1 836
Albendazole 215.2 209.7 161.4 31.2 555
Griseofulvin 220.1 120.4 198.2 52.0 703
Prednisolone 235.4 145.2 205.9 56.4 2752
Indomethacin 160.5 111.1 No peak of melting 2959
Diclofenac 179.1 143.1 No peak of melting 2936
Ritonavir 127.9 92.5 No peak of melting 1203
Statin NCE 73.5 60.0 No peak of melting 108
Docetaxel 173.2 28.7 No peak of melting 3711
SolumerTM technology meets the challenges related to formulation of drugs, belonging to Class II (low solubility) and Class IV (low solubility and permeability) of Biopharmaceutical classification system (BCS). More than 30 lipophilic crystalline active compounds were formulated producing a novel type of solid dispersion. SolumerTM technology is clinically and industrially validated.
The formulation is composed of submicron-particles of API dispersed in multi-polymeric water soluble matrix. SolumerTM confer features for improving drug stability, solubility and bioavailability.
G. Temsin-Krayz, Ph.D, M Averbuch, Ph.D, L. Gitis, Ph.D, Prof. G. Ratner, MD, A Berman, MSc.