INTRODUCTION:

The solubility and permeability of the drug is a key determinant for its oral bioavailability.

Aqueous solubility accounts for up to 50-70 percent of APIs and new medicinal chemicals, resulting in slow absorption and inadequate and variable medication bioavailability¹. When an active substance is taken orally, basically it dissolve in stomach and/or gastrointestinal fluids before it can pass through the GI tract's membranes and enter systemic circulation². As a result, there are two fields of pharmaceutical research that focus on enhancing active agent oral bioavailability: (i) increasing dissolution rate as well as solubility of substances that are weakly water soluble and (ii) enhancing permeability of low permeable drugs.

Oral route is most preferred route of administration of the drug due to numerous reasons like good patient acceptance and low production costs³. Particle size reduction, salt formation, cocrystallization, and the use of surfactants and co-solvents are all methods for improving the dissolving capabilities of weakly aqueous-soluble medicines.

Each of these methods, has its own set of limitations, such as the difficulty in generating salts for neutral and weakly acidic/basic drugs and the addition of surfactants/ co-solvents leads in liquid formulations with recognised commercial viability and patient tolerance issues⁴. Furthermore, despite their high permeability, the bulk of prospective NCEs are absorbed primarily in the small intestine, with absorption reducing substantially after the ileum, indicating that the absorption window is restricted^5,6. As a result, these medications will have a limited bioavailability if they are not entirely released in this gastrointestinal area. Therefore, improving the water solubility of pharmaceutical is primary contemporary difficulties facing by the pharmaceutical industry^7,8,9.

It is feasible to increase bioavailability and prevent side effects by altering these medications' drug release profiles^10,11,12. Solid dispersions have shown to be the most effective methods for increasing the release of poorly soluble medications. These are molecular combinations of low water soluble drugs in water soluble carriers, with a drug release profile determined by the polymer properties¹³. Bioavailability can be improved by enhancing the dissolution rate as well as solubility of the drug in the intestinal fluids, especially for BCS Class II by improving aqueous solubility and, as a result, oral bioavailability and drug dissolution rate.

Classification of solid dispersion on the basis of recent advancement:^1,14

a) First generation Solid Dispersion:

These type of solid dispersions are formed by using crystalline carriers¹⁵. The earliest crystalline carriers utilised in the manufacture of solid dispersions were urea and sugars¹⁶.

Disadvantage: thermodynamically unstable and not releasing the drug as promptly.

b) Second generation Solid Dispersion:

As they are thermodynamically stable, this solid dispersions (SD) were shown to be more effective than first generation solid dispersion method¹⁷. ASDs are distinguished as amorphous solid suspensions or glass solutions based on the state of the drug. Polymeric carrier used may be synthetic polymer or natural polymer¹⁸.

c) Third generation Solid Dispersion¹⁹:

Surfactant carriers serve as carriers in these solid dispersions. Inulin, poloxamer 407, and other surfactants are used in the third generation solid dispersion. For compounds with low solubility, these provide the highest level of bioavailability.

d) Fourth-generation solid dispersion

Controlled Release Solid Dispersions, in contrast to ASDs, are the fourth generation of dispersions (CRSD). Carriers notably Hydroxy Propyl Cellulose (HPC) and Eudragit RS are used to keep physiologically short-half-life medications on the market. Its major objective is to extend medication release and increase solubility at a regulated rate²⁰.

METHODS OF PREPARATION OF SOLID DISPERSION²¹:

1) Solvent Evaporation method.

2) Kneading Method.

3) Fusion Method:

i. Simple fusion.

ii. Hot-melt extrusion.

iii. Microwave induced.

iv. KinetiSol®

4) Solvent evaporation:

i. Simple solvent.

ii. Spray drying.

iii. Lyophilization

iv. Electrostatic spinning

v. Fluid-bed coating

5) Miscellaneous:

i. Solvent-based methods.

ii. Solvent-melt.

iii. Supercritical Co2.

iv. Co-precipitation

1. Solvent Evaporation Technique:

The main technique entails dissolving the medication and carrier in a volatile solvent until a homogeneous combination is achieved²². After that, the integrated amount of solvent is calculated to obtain SD. Further, it is vaporized in a variety of conditions, including ambient, heating, and even freezing temperature. Solvent evaporation (SE) techniques are frequently used in both small labs and large-scale companies. The evaporation method selected is determined on the ingredient's stability. Furthermore, the surfactant concentration is important because the evaporation process creates a diffusion layer that might slow medication release. The evaporation speed, the kind of solvent or co-solvent, and the evaporation technique utilised can all have an impact on yield uniformity; Hu et al. found that using a rotary vacuum evaporator increased homogeneity considerably²³. Scale-up procedures with an efficient output, such as spray-drying, freeze-drying, and high-speed electrospinning, can be used to operate the solvent evaporation technique. Hot plate stirring, rotary evaporation, single-needle electrospinning, and lab spray-drying are all small-scale processes that can be used^21.

Sr. No	Physical Structure	Drug-carrier miscibility	Stability	Amorphous content	Dissolution Enhancement
1	Scanning electron microscopy	FT-IR spectroscopy	Saturated stability studies	Hot stage microscopy	Dissolution
2	Surface area analysis	Powder X-Ray diffraction	Isothermal calorimetry	DSC (MTDSC)	Intrinsic dissolution
3	Raman microscopy	Differential scanning calorimetry	DCS (Temperature recrystallization)	Polarised light optical microscopy	Dissolution in bio-relevant media
4	Inverse gas chromate-graph	Raman spectro-scopy	Humidity studies	Powder X-ray diffraction	Dynamic solubility
5	Atomic force microscopy			Humidity stage microscopy

MARKETED SOLID DISPERSION PRODUCTS^29,30,31

The following are some examples of commercially available solid dispersions:

1) Solid dispersion of Troglitazone marketed by Parke Davis.

2) Solid dispersion of itraconazole by Sporanox.

3) Gris-PEG®, solid dispersion of griseofulvin marketed by Novartis.

CONCLUSION:

Commonly used solid dispersions methods like solvent evaporation and kneading are one of the most promising ways for increasing the oral bioavailability of medicines that are poor in water solubility. Bioavailability may be considerably improved by lowering drug particle size to an absolute minimum and thereby boosting drug wettability.

REFERENCE:

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Received on 11.07.2022 Modified on 22.08.2022

Asian J. Res. Pharm. Sci. 2023; 13(2):167-170.

DOI: 10.52711/2231-5659.2023.00029