A Review on Different Solubility Enhancement Techniques of Ticagrelor

Abstract

Solubility is characterized as the sum of substance that passes into the solution to form a saturated solution at steady temperature and pressure. Solubility can be framed in terms of the maximum volume or mass of the solute that breaks up in a given volume or mass of a solvent. 2 An increase in solubility can be achieved by various methods such as Salt formation, Complexation, Micronization, 4 Solid Dispersion, altering the pH, co-solvency, co-crystals, polymeric micelles, etc. 5 A highly efficacious technique is the conversion of a crystalline drug to its amorphous form. Amorphous drugs have better solubility than crystalline drugs due to their structure, increased surface area, and better wettability. 6 The amorphous state has better solubility as it has higher entropy, enthalpy, volume, and free energy when compared to its crystalline structure. 7 TICAGRELORTicagrelor is classified as an anti-platelet aggregator, which reversibly binds to the P2Y12 receptor and acts by antagonizing the binding of adenosine phosphate to the P2Y12 receptor resulting in decreased uptake of adenosine. It is a direct-acting and immediate-release drug taken orally. Both the active drug ABSTRACT Ticagrelor is a BCS class IV drug that inhibits platelet action by reversibly binding to the P2Y12 receptor. One of the major challenges faced by the class IV (low solubility, low permeability) drug is the lower dissolution rate leading to low bioavailability. The bioavailability of the marketed formulation of ticagrelor is approximately 36%. Researchers have come up with various techniques to improve the BCS class II and IV drug formulations as an integral part of the development of the pharmaceutical sciences. An increase in solubility can be achieved by various methods such as Salt formation, Complexation, Micronization, Solid Dispersion, altering the pH, Co-solvency, co-crystals, polymeric micelles, etc. A highly efficacious technique is converting a crystalline drug to its amorphous form. An extensive literature search was conducted using various databases like science direct, Taylor and Francis, Springer to extract relevant articles. Keywords like "Ticagrelor", "low permeability", "P2Y12 receptor inhibitor" were used for the literature search. Relevant articles were screened and referred for further study. This article discusses the techniques employed to increase the solubility of ticagrelor, thus highlighting the research conducted and reported. The increase in bioavailability of ticagrelor could be seen when formulated as nanoparticles, co-crystals, ticagrelor loaded self-micro emulsifying and nano emulsifying drug delivery system, solid dispersion, etc. the conversion of the crystalline drug into amorphous drug is a highly recommended approach to increase the solubility of ticagrelor which can be seen in cases of co-crystals and solid dispersion formulation.

Micronization Techniques for Solubility Enhancement of Aceclofenac as a potential Solubility Enhancement Approach

“…The crystal structure of pure Aceclofenac(ACL) and micronized Aceclofenac (ACLM) was confirmed by DSC, FT-IR and XRD studies [20][21][22][23] .…”

“…The thermal behaviour of pure Aceclofenac and micronized Aceclofenac selected solid dispersion formulations were studies by Differential Scanning Colorimeter (DSC, DSC 822 e Software STAR e 16.10, Metller). In this study, different samples were heated at 10°C/min over a temperature range of 40-250°C under flow of nitrogen (60ml/min) in pierced aluminium pans and crystallinity of Aceclofenac was compared with prepared solid dispersions [20][21][22][23] .…”

“…The spectrum was recorded between 4000 -400cm -1 . The FT-IR spectra of the different samples were compared with pure Aceclofenac spectra [20][21][22][23] .…”

Crosslinked PVA-g-poly(AMPS) Nanogels for Enhanced Solubility and Dissolution of Ticagrelor: Synthesis, Characterization, and Toxicity Evaluation

“…Additionally, TGR exhibits a rapid offset of the antiplatelet effect compared to prasugrel, thus reducing the risk of side effects such as bleeding . Because of the aforementioned reasons, TGR is currently preferred over other antiplatelets in clinical guidelines. , TGR has been reported to have low aqueous solubility (10–15 μg/mL) and low permeability, leading to a low oral bioavailability of ≈36% . Therefore, the development of an adequate drug delivery system for enhancing the solubility of TGR and, ultimately, efficient ACS therapy is extremely important.…”

“… 16 , 18 TGR has been reported to have low aqueous solubility (10–15 μg/mL) and low permeability, leading to a low oral bioavailability of ≈36%. 19 Therefore, the development of an adequate drug delivery system for enhancing the solubility of TGR and, ultimately, efficient ACS therapy is extremely important.…”