Purpose This study aimed to ensure the convenience of administration and reproducibility of efficacy, regardless of the meal, by improving the solubility of rivaroxaban (RIV). Methods RIV is a non-vitamin K antagonist oral anticoagulants that exhibits a coagulation effect by directly inhibiting coagulation factor Xa. However, RIV has a very low solubility; therefore, it must be administered with a meal at high doses. We used a drug- hydroxypropyl-beta-cyclodextrin (CD)-water-soluble polymer triple complex (R-C-P complex) to solubilize RIV. Using Minitab, we evaluated the effect of each factor on RIV solubility and developed an optimal R-C-P complex formulation. The amount of CD, amount of polymer, and polymer type were set as the independent variables X 1 , X 2 , and X 3 , respectively. RIV solubility (Y 1 ) and dissolution rate for 45 min in pH 4.5 medium (Y 2 ) and pH 1.2 medium (Y 3 ) were set as response variables. Results The most efficient RIV solubilization effect was obtained from the composition using CD and HPMC 2208, and physicochemical properties and dissolution parameters were analyzed. RIV in the R-C-P complex was present in an amorphous form and showed high solubility. Unlike commercial products, it showed a 100% dissolution rate. The R-C-P complex formulation secured high RIV solubility and 100% release regardless of pH. Conclusion The results imply that high-dose RIV can be administered regardless of the meal, reducing the risk of changing the drug effect due to the patient’s administration mistake.
Pirfenidone (PRF) is an anti-fibrotic agent that has been approved by the Food and Drug Administration (FDA) for the treatment of mild to moderate idiopathic pulmonary fibrosis.However, the current oral administration dosing regimen of PRF is complex and requires high doses. Patients are instructed to take PRF three times daily, with each dose consisting of up to three capsules or tablets (600 mg/day or 1.8 g/day of PRF) taken with food. To improve the dosing regimen, efforts are being made to develop an extended-release tablet with a zeroorder release pattern. In this study, two types of extended-release matrix tablets were compared: non-channeled extended-release matrix tablets (NChMT) and channeled extendedrelease matrix tablets (ChMT). In vitro release tests, swelling and erosion index, rheology studies, and X-ray microcomputed tomography (XRCT), were conducted. The results indicated that ChMT maintained a zero-order release pattern with a constant release rate, while NChMT exhibited a decreased release rate in the latter half of the dissolution. ChMT exhibited accelerated swelling and erosion compared to other formulations, and this was made possible by the presence of channels within the tablet. These channels allowed for thorough wetting and swelling throughout the entire depth of the tablet. The formation of channels was confirmed through XRCT images. In conclusion, the presence of channels in ChMT tablets increased the rate of swelling and erosion, resulting in a zero-order release pattern. This development offers the potential to improve the dosage of PRF and reduce its associated side effects.
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