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The in vitro release test (IVRT) is a powerful tool for prediction of the impact of formulation excipients on the drug release profile as well as lot-to-lot uniformity. We have determined and compared the release profile of diclofenac (a non-steroidal anti-inflammatory agent) from marketed topical formulations using an in-line cell automated diffusion system. We describe the advantages of the automated diffusion system along with factors influencing the in vitro release, such as type of membranes and receptor solution. A validated reverse phase-high performance liquid chromatography (RP-HPLC) method at a wavelength of 276 nm in the range of 0.200 to 100.000 µg/mL was used for effective analysis of in vitro release samples, with good sensitivity and precision. A linear relationship was found, with a coefficient of determination (R 2) ≥ 0.90 for diclofenac semisolid matrices. Among all similar strength formulations, the maximum release rate was obtained from Volini gel and Voltaren Forte, having 1% w/w and 2% w/w diclofenac, respectively.

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.

Objective: The study aims to enhance the solubility and dissolution of ticagrelor by formulating an amorphous solid dispersion using the hot melt extrusion technique. Methods: Solubility of ticagrelor is very limited in water and buffers of pH 1.2 to 6.8, which is one of the prime reasons for its low oral bioavailability. Amorphous solid dispersions were prepared using the Hot Melt Extrusion technique using different polymers, plasticizers, and surfactants. The formulation is optimized based on the level of polymer in the formulation. The final formulation of Ticagrelor Amorphous Solid Dispersion is made with a drug-polymer ratio of 1:3, keeping the plasticizer level at 10% of the polymer along with a surfactant Sodium Lauryl Sulfate. Results: The formulation showed an increase in solubility of 193.95-times in water, 50.71-times in 0.1 N HCl, 332.74-times in pH 4.5 acetate buffer, and 85.20-times in pH 6.8 phosphate buffer as compared to the pure drug. The drug release of the final formulation was found to be 70.0±4.4%, 55.4±1.1%, 35.5±2.1%, and 30.0±0.8% at 90 min, while the reference product showed a release of 9.4±1.1%, 20.7±0.5%, 8.4±0.3%, and 7.8±0.2% at 90 min in water, 0.1 N HCl, pH 4.5 acetate buffer and pH 6.8 Phosphate Buffer respectively. The drug release of the final formulation was found to be 99.1±3.8% at 60 min in 0.2% w/v Polysorbate-80 in water. Conclusion: In the present study, the amorphous solid dispersion of the poorly-soluble drug ticagrelor was successfully prepared. The polymer, Plasdone S630, is considered the most suitable with ticagrelor for formulating amorphous solid dispersion using Hot Melt Extrusion technology to increase the solubility and dissolution of the drug.

Excipients play a very important role in the release pattern of an active pharmaceutical ingredient from topical semisolid dosages forms, and their physical and chemical properties can influence the release. The aim of this paper was to provide a validated, sensitive, and reproducible method to assess the in vitro release rate of an antifungal drug (Terbinafine) from controlled drug delivery systems (cutaneous and film-forming solution) and to prove product sameness. The samples obtained from in vitro testing were analyzed through a high performance liquid chromatographic (HPLC) system coupled with UV spectrometer at a wavelength of 283 nm. A Franz diffusion cell (FDC) system was used for the dissolution test. We recorded the drug release from the formulation for 6 hours. The release rate obtained from cutaneous and filmforming solutions were compared statistically to depict the sameness. The results met the relevant acceptance criteria (i.e., 90% confidence interval, falling within the limits of 75-133%) as defined in the scale-up and post-approval changes (SUPAC-SS) guidance. The obtained results confirm the competence of the IVRT method for the assessment of product sameness.