Enhancement of water dissolution rate of tetra Tert-butyl Zn (II) Phthalocyanine

using solid dispersions with Pluronic F127: Proof of concept

protocole solide dipersion with PEG 4000

Preparation of solid dispersions

Solid dispersions were prepared by using the fusion method: appropriate amounts of tetra Tert-butyl Zn (II) Phthalocyanine
(10% w/w 10 mg/90 mg PEG) were added to the previous molten carrier 57 0C and then stirred with the aid of a stirring
rod until the total dispersion of the PS. During the process, temperature was
maintained at 90 0C . After slow cooling to ambient T, solidified samples were milled
to obtain powder and sieved (500 mm).

Figure 1: Chemical structures 2,9,16,23-

Tetra-tert-butyl-29H,31H-phthalocyanine
zinc (II)

Solubility and dissolution rate in the GI fluids constitute the limiting steps of the bioavailability of orally-administered drugs
considered as type II, according to the Biopharmaceutical Classification System (BCS) [1], e.g. all those APIs with an adequate
permeability but a low solubility and/or dissolution rate. Over the years, many strategies were proposed and applied to
overcome these limitations, including salt formation, cosolvents, complexation, use of metastable polymorphs, amorphous
phases, cocrystals, nanosizing and combination with carriers as solid dispersions [2-8]. Among them, solid dispersions offer
some significant advantages, such as pH independent release [9], inexpensive and easy manufacture, process reliability, low
excipient cost and easy access to a wide variety of them.

Protocol

1
Preparation of solid dispersions

Solid dispersion will be prepared by fusion method. To this end, Zn (II) tetra, tert-butyl phthalocyanine and Pluronic F127
will be mixed and heated up to 70 ◦C. The mixture will be homogenized by stirring during 5 h at 70 ◦C. After that the dispersion
will be allowed to solidify at room temperature. The Zn (II) tetra, tert-butyl phthalocyanine content in the solid dispersion
will be 10 wt%. Corresponding physical mixture of Zn (II) tetra, tert-butyl phthalocyanine with Pluronic F127 will be prepared
by blending the components. Solid dispersion and physical mixture will be sieved using a sieve of 80 μm and will be stored in
desiccator at room temperature until use.

Characterization of the samples

- The particle size and morphology will be examined with scanning electron microscope.
- The powder X-ray diffraction (PXRD) will be performed
- Thermal characterization of the samples will be performed using differential scanning calorimeter DSC
- FTIR spectra will be recorded in the range of 400–4000 cm.

Solubility study
- UV-vis absorption spectroscopy in water will be performed
- Fluorescence spectroscopy in water and fluorescence quantum yield in water will be performed
- Singlet oxygen quantum yield in water will be performed

References
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