アメリカの薬物送達と治療学ジャーナル オープンアクセス

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Pharmaceutica 2016 カンファレンス: 既存薬と新薬候補を含む結晶性超分子システムの物理化学的特性評価 - Mino R. Caira - ケープタウン大学

ミノ・R・カイラ

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薬物粒子を含む結晶性超分子構造、例えば、鎮静溶媒和物、共結晶、および薬物混合物は、新しい多分子構造を示し、その薬学的応用特性（例えば、液体溶解性、強度、可塑性）が未処理の薬物よりはるかに優れている可能性があるため、注目度が高まっています。合成薬物の場合、これは特許寿命の延長につながる可能性がありますが、新薬リードの場合、このような「超分子誘導体」の製造への早期介入は、さらなる開発のための最も有望な候補の決定を促進する可能性があります。これらの多分子結晶構造の物理化学的描写は、原子レベルでの化学量論的割合、熱力学的安定性、および補助特性を構築するために不可欠ですが、単一分子構造（例えば、多形性純粋薬物）を扱うときに経験するよりも多くの問題を引き起こすことがよくあります。このような問題は、付加的な溶解性（含有量の変動や基本的な問題など）や、異種分子相互作用の概念の明確な理解における課題（共結晶や塩の認識など）に関連している可能性があります。医薬有効成分（API）は、多形、溶媒和物、水和物、塩、共結晶、不均一な固体など、さまざまな固体構造で存在する可能性があります。各構造は、薬剤のバイオアベイラビリティ、製造性、洗浄性、信頼性、その他のパフォーマンス特性に大きく影響する可能性のある、独自の物理化学的特性を示します。

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. Co-crystallization is an appearance of guided self-get together of various segments. Co-precious stones have been portrayed of different natural substances throughout the years and given different names, for example, expansion mixes atomic edifices and heteromolecular co-gems. Notwithstanding naming show, the fundamental importance is that of a multi-part precious stone where no covalent synthetic change of the constituents happens because of the gem development. Pharmaceutical co-precious stones can be characterized as crystalline materials included an API and at least one of a kind co-gem formers, which are solids at room temperature. Co-precious stones can be developed through a few sorts of collaboration, including hydrogen holding, p stacking, and vander Waals powers. Solvates and hydrates of the API are not viewed as cocrystals by this definition. In any case, co-gems may incorporate at least one dissolvable/water atoms in the gem cross section. Co-precious stones frequently depend on hydrogenbonded gatherings between nonpartisan particles of API and other segment. For nonionizable mixes co-precious stones upgrade pharmaceutical properties by alteration of synthetic soundness, dampness take-up, mechanical conduct, solvency, disintegration rate and bioavailability.

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.

The degree of polymorphism of pharmaceutical is restricted to the bunch of the diverse gem structures. Essential distinction among solvates and co-gems is the physical condition of the individual segments. On the off chance that one part is fluid at room temperature, at that point the precious stones are assigned solvates, though on the off chance that the two segments are solids at room temperature, at that point the gems are assigned as co-gems. Solvates are ordinary since they happen as a fortunate consequence of crystallization from arrangement and can possibly improve tranquilize disintegration rate, as appeared for the solvated types of spironolactone. Solvated precious stones anyway are frequently precarious, prompting desolvation during capacity and such dissolvable misfortune may prompt the nebulous stage solidifying into less solvent structures. Dissolvable levels in solvated precious stones are likewise frequently at fixations that are not worthy to administrative specialists and which may likewise have toxicological outcomes. Co-gems, be that as it may, will in general be a result of increasingly reasonable plan and are progressively steady, especially as the co-taking shape specialists are solids at room temperature. Similarly as with other crystalline frameworks, polymorphic co-precious stones are normal. At any rate 20 have been accounted for to date, including caffeine and glutaric corrosive polymorphic co-gems while co-precious stones are characterized by a solitary stage (miscible) multi-part framework in the crystalline state, in the formless state they have been alluded to as atomic scatterings with cooperations between the segments recognizing them from strong scatterings.

共結晶は強散乱を伴わないが、共結晶を結晶から分離しようとするときに強散乱が発生することがある。強散乱という一般的な用語は、溶解（混合）法、溶解法、または混合溶解法によって形成された、固体状態のアイドルキャリア内の1つ以上の活性成分の分散を指す。分子サイズを縮小し、薬物の分解速度と吸収を高める強散乱法は、1961年に初めて認識された。強散乱の調製では、結晶状態を形成する能力が低く、結晶化する傾向が顕著な薬物は、結晶化を意図的に阻止することによって不透明にされることが多い。

その後のさらなる合成法には、凍結乾燥やスプレー乾燥による急速沈殿、自然に定義されていない親水性ポリマーの視野内での超臨界液体の使用、液化除去などの方法の使用などが含まれる。この紹介では、これらの問題に対処するために使用される主要な方法として、粉末と単一宝石の両方に対する熱分析とX線回折法の使用に焦点を当てます。活性医薬成分の共宝石や生物活性原子のシクロデキストリン考慮構造などの超分子構造へのそれらの応用について概説します。言及される構造の宝石多形の普遍的な発生と、段階識別証明における粉末X線回折の適用の限界は、強調されるべき密接に関連する点です。

バイオグラフィー

ミノ・カイラは、2005 年よりケープタウン大学 (UCT) の超分子化学研究センターの所長を務めています。2014 年に物理化学教授を退任し、その後 UCT の化学部門の上級研究員に任命されました。専門分野は、薬物多形体の固体化学と、医薬品有効成分を含む新しい多成分系です。国際誌に 300 本以上の論文を発表しており、2009 年からは Journal of Pharmaceutical Sciences の編集諮問委員会に所属しています。