The structure of Vardenafil is given below:
Vardenafil is a solid that is practically insoluble in water and very slightly soluble in some organic solvents such as methanol, ethanol and acetone. US Pat. No. 6,841,167 discloses that the solubility of Vardenafil in water is approximately 2 μg in 1 ml of water.
Various techniques have been undertaken in an attempt to overcome the observed poor solubility of Vardenafil in water. US Pat. No. 6,841,167 discloses a pharmaceutical formulation containing Vardenafil in the form of a “free drug” together with a diluent, a lubricant, a hydrophilic binder and a disintegrant. When attempting to prepare Vardenafil formulations with possible improved bioavailability, soft capsules containing Vardenafil, suspended in a pharmaceutically acceptable solvent, are presumably created.
Another technique used to improve solubility is described in US Pat.
No. 6753789787, and includes the preparation of formulations by Vardenafil coprecipitation, in which a homogeneous mixture of & quot; Vardenafil and the carrier in a water immiscible solvent and possibly with water are coprecipitate from the “homogeneous mixture using an aqueous” coprecipitation medium in which the carrier is substantially insoluble.
The US patent is included in the United States Federal Food and Drug Administration’s Orange Book for the Cialis product and is clearly intended for a company that sells on the Cialis market.This patent is presumably referring to the shredded form of the free drug Vardenafil, containing particles of the compound in which at least 90% of the particles have a size of less than about 40 microns. Preferably, at least 90% of the particles have a size of less than 10 microns.
The above-described methods for increasing the bioavailability of Vardenafil suffer from economical and safety disadvantages.
US Patent No. 6,821,975 suggests carrying out fine grinding, which can be time-consuming, and there may also be safety-related problems due to the finely divided powder obtained therefrom. US Patent No. 5,985,326 suggests the use of significant amounts of an organic solvent that is not desirable for the environment. Thus, a method that uses large drug particles (with d (0.9) of 40 microns or more) while maintaining the desired bioavailability will improve the economy and safety of the production process of Vardenafil tablets.
Levy et al. (Levy et al.) Reported the effect of starch on the dissolution rate of salicylic acid from tablets prepared by double pressing (Levy, G. et al, J. Pharm., Sci., 1963, 52, 1047). It was reported that an increase in the starch content of 5 to 20% increased the dissolution rate of salicylic acid three-fold. This observation was attributed to faster disintegration of tablets with a higher content of starch in them. In 1966, Fynholt et al. (Finholt et al.) Observed that finely ground starch particles added to phenobarbital tablets increased the rate of dissolution of phenobarbital from the tablets. Coming to a different conclusion than suggested by Levy et al. (Levy et al.), Fynholt et al. (Finholt et al.) Suggested that starch acted as a coating for phenobarbital crystals and imparted to it a hydrophilic property that improved the contact between the phenobarbital particles and the aqueous dissolution medium (Finholt, P. Medd Norsk Farm, Selsk, 1966, 28, 238 ).
Starch is an ordinary component of tablets, where it is used for a number of reasons.
It is generally used, for example, as a diluent, binder, disintegrant, and glidant. The diluents increase the volume of the solid pharmaceutical composition and can make the pharmaceutical dosage form containing the composition more convenient to handle for the patient and the caregiver.
Binders help bind the active ingredient and other constituents together, for example, during the granulation and compaction steps.
The disintegrants accelerate the disintegration of the tablet in the patient’s stomach, usually by penetrating water into the tablet, causing it to swell, thereby leading to the disintegration of the tablet info Vilitra.net smaller parts (resulting in a larger surface area).
Sliding agents improve the flowability of the powder compositions by forming a coating on the particle surfaces.