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難溶藥物的溶解度增強和開發奈米混懸劑的實驗方法設計

阿爾普圖格·卡拉庫丘克

諸如可溶性、室溫下的穩定性、可溶性、賦形劑的相似性和光穩定性等邊界範圍在有效的藥物治療計劃中發揮基本作用。迄今為止，透過藥物揭示計劃生產的新合成元素中有超過 40% 是親脂性或無效的水溶劑混合物。有許多計劃方法可以解決藥物償付能力低和生物利用度低的問題。常用的方法包括微粉化、使用油脂組合、使用入口促進劑或助溶劑、界面活性劑分散策略、鹽生成、沉澱等，然而，這些策略在改善溶劑不足的藥物的溶解能力方面的效用受到限制。其他方法包括脂質體等囊泡結構、固體分散、乳液和微乳液策略以及環糊精的考慮結構，這些結構顯示出作為藥物傳遞結構的有利影響，但這些方法的嚴重問題是缺乏與所有藥物的全面相關性。藥物原子的較差的液體溶解能力問題限制了透過口服或皮膚途徑的鎮靜劑保留，並且最終由於疏水性而降低了生物利用度。此外，找出溶解不充分的藥物以建立償付能力以獲得充分的作用也是一項重大挑戰。一些新的藥物申請人透過高通量篩選來確定目標受體幾何形狀，具有高亞原子質量和高 Log P 值，這增加了不溶性。

根據生物製藥分類系統，II 類和 IV 類藥物被視為無效溶劑。物理變化（微粉化、多晶型開發、強散射、環糊精結構、天然可溶物的利用）、混合物調整（前藥規劃、鹽結構）或奈米技術方法（膠束、脂質體、奈米乳液等）被認為可以克服低水位。物理和混合物改變有一些缺點，例如，與每種藥物動態物質不相關、無法提供足夠的擴展浸泡溶解能力或導致作用喪失。奈米技術可用於解決與前面描述的不同方法相關的問題。奈米技術的特點是 10-9 m 奈米尺度的科學和設計。

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.

品質源自於設計的具體能力稱為實驗設計 (DoE)。美國能源部方法實際上分析了計劃範圍內因素之間的關聯，並透過考慮理想的項目屬性來促進定義的發展。美國能源部方法透過減少測試數量來幫助制定奈米懸浮計劃，從而帶來成本和效率。