Journal américain de l'administration de médicaments et de la thérapeutique Libre accès

Abstrait

Physicochemical characterization of crystalline supramolecular systems containing established drugs and new drug candidates

Mino R. Caira

Crystalline supra sub-atomic frameworks containing drug particles, for instance sedate solvates, co-precious stones and consideration mixes, are getting a charge out of expanding consideration as they speak to new multi-segment shapes whose pharmaceutically applicable properties (for example fluid solvency, strength, developability) might be altogether more good than those of the untreated medication. On account of set up drugs, this could convert into expanded patent life, while for new medication leads early intercession in producing such 'supramolecular subordinates' could encourage the determination of the most encouraging contenders for additional turn of events. Physicochemical portrayal of these multi-part crystalline stages to build up their stoichiometric piece, thermodynamic dependable qualities and auxiliary nature at the atomic level is fundamental yet can frequently present a bigger number of difficulties than those experienced when managing single-segment frameworks (for example polymorphically unadulterated medications). Such difficulties might be related with included dissolvable (for example content fluctuation and basic issue) and with challenges in unequivocal task of the idea of heteromolecular communications (for example recognizing co-gems and salts). Pharmaceutical dynamic fixings (APIs) can exist in an assortment of unmistakable strong structures, including polymorphs, solvates, hydrates, salts, co-precious stones and nebulous solids. Each structure shows one of a kind physicochemical properties that can significantly impact the bioavailability, manufacturability cleaning, dependability and other execution attributes of the medications.  

Strong structure revelation and configuration relies upon the idea of the atom of intrigue and sort of physical property challenges looked in its turn of events. The favored strong structure is commonly the thermodynamically most stable crystalline type of the compound. Notwithstanding, the steady gem type of the parent compound may show insufficient solvency or disintegration rate bringing about poor oral retention, especially for water-insoluble mixes. For this situation, elective strong structures might be examined. For ionizable mixes, planning of salt structures utilizing pharmaceutically worthy acids and bases is a typical system to improve bioavailability. Like the parent compound, pharmaceutical salts may exist in a few polymorphic, solvated and additionally hydrated structures. Precious stone building is commonly viewed as the structure and development of crystalline atomic solids with the point of affecting material properties. A chief instrument is the hydrogen bond, which is liable for most of coordinated intermolecular associations in sub-atomic solids. Co-gems are multi-part precious stones dependent on hydrogen holding cooperations without the exchange of hydrogen particles to frame salts; this is a significant component, since Bronsted corrosive base science isn't a necessity for the arrangement of a co-gem.

A relationship can be attracted to salt determination in which pKa contentions are utilized to choose corrosive base matches that can be changed over to salt mixes. Science shows that a pKa contrast of in any event two units (between a corrosive and a base) is required to shape a salt that is steady in water. It is likewise essential to recollect that salt development is commonly aimed at a solitary acidic and fundamental utilitarian gathering. Interestingly co-precious stones can at the same time address various useful gatherings in a solitary medication particle. Furthermore space isn't restricted to twofold mixes (corrosive base sets) since tertiary and quaternary co-precious stones are reasonable one. One intriguing thing was seen that co-precious stones give an incredible way to tailor the ideal solvency and disintegration pH reliance of APIs, in any event, when the API is a non-ionizable particle. Their application to supramolecular frameworks, for example, co-gems of dynamic pharmaceutical fixings and cyclodextrin consideration edifices of bioactive atoms will be outlined. Firmly related points to be featured are the universal event of gem polymorphism for the frameworks being referred to and the restrictions of the utility of powder X-beam diffraction in stage distinguishing proof.