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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難溶性薬物の溶解性向上: ナノ懸濁液を開発するための実験計画法 - Alptug Karakucuk

アルプトゥグ・カラクチュク

溶解性、室温での安定性、溶解性、賦形剤との類似性、光安定性などのさまざまな特性が、医薬品の効果的な設計において重要な役割を果たします。現在までに、医薬品開発プロセスで製造されている新しい合成成分の 40% 以上が親油性または水と溶媒の混合効率が低いものです。医薬品の溶解性およびバイオアベイラビリティが低いという問題を解決するために、さまざまな設計手法が利用可能です。従来の手法には、微粉化、油性溶液の使用、入口エンハンサーまたは共溶媒の使用、界面活性剤分散法、塩生成、沈殿などがありますが、これらの手法は、溶解性が不十分な医薬品の溶解性改善には限定的な効果しかありません。その他の方法としては、リポソームのような小胞構造、固体の分散、エマルジョンおよびマイクロエマルジョン法、およびシクロデキストリンとの相互作用構造があり、これらは薬剤送達システムとして有益な効果を示しますが、これらの方法の大きな問題は、すべての薬剤に包括的に関連がないことです。薬剤分子の液体溶解性の低さの問題は、経口または経皮経路での鎮静剤の保持を制限し、最終的には疎水性のためにバイオアベイラビリティを低下させます。さらに、溶解性が不十分な薬剤を特定して溶解性を高め、十分な効果を得ることは大きな課題です。ハイスループットスクリーニングによってターゲット受容体構造について検討されているいくつかの新しい薬剤候補は、不溶性を高める高いサブ原子質量と高いLog P値を持っています。

バイオ医薬品分類システムによると、クラス II および IV の医薬品は溶解性が低いとされています。 物理的改変 (微粒子化、多形形成、固体散乱、シクロデキストリン構造、天然溶解性物質の使用)、化学改変 (プロドラッグ設計、塩構造)、またはナノテクノロジー手法 (ミセル、リポソーム、ナノエマルジョンなど) は、低水溶性の問題を克服すると考えられています。 物理的改変および化学改変には、すべての医薬品有効成分に関連しない、十分な拡張浸漬溶解性が得られない、または作用が失われるなど、いくつかの欠点があります。 ナノテクノロジーは、前述のさまざまな手法に関連する問題を解決するために使用できます。 ナノテクノロジーは、10–9 m のナノスケールで行われた科学と設計として定義されます。

In the most recent years, it is viewed as that tranquilize nanosuspensions are one the best ways to deal with figure ineffectively dissolvable mixes. Nanosuspensions are scattered frameworks which have nanometer extend, normally 200-600 nm, unadulterated medication particles. They contain least measure of settling specialists, for example, surfactants as well as polymers. Nanosuspensions can be delivered by precipitation, wet processing, high weight homogenization, or blend of these strategies. With remarkable properties of nanosuspensions by giving expanded surface region of medication articles, they can improve immersion solvency and disintegration pace of ineffectively dissolvable medications and thus oral or dermal bioavailability. The medication microparticles/micronized sedate powder is moved to tranquilize nanoparticles by methods like Bottom-Up Technology and Top-Down Technology. Nanosuspensions are submicron colloidal scatterings of nanosized tranquilize particles balanced out by surfactants. Nanosuspensions comprise of the ineffectively water-dissolvable medication with no grid material suspended in scattering. These can be utilized to upgrade the dissolvability of medications that are ineffectively solvent in water just as lipid media. Because of expanded solvency, the pace of flooding of the dynamic compound increments and the most extreme plasma level is arrived at quicker. This methodology is helpful for particles with helpless solvency, helpless porousness, or both, which represents a critical test for the formulators. The diminished molecule size delivers the chance of intravenous organization of inadequately dissolvable medications with no bar of the blood vessels. The suspensions can likewise be lyophilized and into a strong lattice. Aside from these points of interest, it additionally has the upsides of fluid definitions over others. Pharmaceutical nanosuspensions of medications are nanosized, heterogeneous watery scatterings of insoluble medication particles balanced out by surfactants. Conversely, nanoparticles are either polymeric or lipid colloidal transporters of medications. Nanosuspension procedure is the main alternative accessible, when a medication atom has numerous inconveniences, for example, failure to shape salt, huge sub-atomic weight and portion, high log P and softening point that obstruct them in creating appropriate details. Nanosuspensions can fathom such extraordinary medication conveyance issues related with the dynamic pharmaceutical fixings (API) by holding it in a translucent state while empower them with expanded medication stacking during detailing advancement. Obliging enormous medication sum with least portion volume has extra advantages in parenteral and ophthalmic medication conveyance framework inferable from the minimization of unnecessary utilization of unsafe non-watery solvents and extraordinary pH. Different focal points incorporate expanded dependability, continued arrival of medication, expanded viability through tissue focusing on, least first pass digestion and profound lung affidavit. The soundness of the submicron particles accomplished in the nanosuspension is for the most part ascribed to the uniform molecule size, which is shaped by various assembling procedures. Particles of nanosuspensions must stay unaltered in size all through its timeframe of realistic usability else it can start unconstrained precious stone development. In this manner, keeping up the uniform molecule size dispersion can frustrates the nearness of differing immersion dissolvability and accordingly repress any precious stone development because of Oswald aging impact. Nanosuspension of the medication can likewise be accomplished by weakening of emulsion, along these lines causing full dissemination of scattered stage into the constant stage bringing about the creation of nanosuspension. Microemulsion can be treated in comparative way for the creation of nanosuspensions. The impact of globule size and measure of surfactant (s) on the medication take-up of inward stage ought to be analyzed to create ideal medication stacking. Nanosuspension created by such strategies must be cleared from following solvents and different fixings by methods for ultrafiltration procedure to make it helpful for organization. Lyophilization of the nanosuspensions will be done to improve the physical and synthetic soundness and to conquer the incongruencies between the different detailing segments. Sanitization of the nanosuspensions should be possible either by film filtration (< 0.22 μm), steam heat cleansing or gamma illumination. Writing proposes that enhancement of base up nanosuspension approach requires fitting choice and setting appropriate convergence of excipients, for example, surfactant and polymer.

Qality by Design の具体的な機能は、実験計画 (DoE) として知られています。DoE アプローチは、計画領域内の要因間の関係を物理的に分析し、理想的な製品属性を考慮して定義の開発を可能にします。DoE アプローチは、コストと効率をもたらすテストの数を減らすことで、ナノサスペンション計画の作成に役立ちます。