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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モデリングツールを駆使した開発初期段階における非晶質固体分散処方の最適化

キエレマテン

問題の説明:

アモルファス固体分散体 (ASD) は、溶解性、濡れ性、崩壊速度を高めることで、水に溶けにくい活性医薬品成分 (API) のバイオアベイラビリティを向上させるための製剤設計手法です。熱溶解法 (HME) による ASD 製剤の効率的な製造には、適切な API 含有量、賦形剤、取り扱い温度などの選択が必要です。また、製剤の重要な品質特性 (耐用期間中の安定した製品性能を保証するための長期物理的信頼性など) を決定する上で、製剤のインターフェイスの強度も重要です。HME の実現可能性と危険性評価のための考えられる最大の薬剤含有量と賦形剤、および製造された ASD の長期物理的強度を特定することは非常に困難であり、いくつかの製剤試験と長時間の安全性試験が必要になります。アモルファス固体分散体 (ASD) は、開発中の水溶性の低い医薬品混合物にますます頻繁に使用されています。これらのシステムは、ポリマーでバランスをとった不特定の活性医薬成分で構成され、物理的および構造的安定性が向上したシステムを作成します。ASD は、通常、機能する医薬成分の透明な溶解性を向上させる方法と見なされます。

This survey will examine techniques for arrangement and portrayal of ASDs with an accentuation on comprehension and anticipating security. Hypothetical comprehension of super immersion and foreseeing in vivo execution will be focused. Moreover, a synopsis of preclinical and clinical advancement endeavors will be introduced to give the peruser a comprehension of dangers and key entanglements when building up an ASD. Nebulous strong scatterings (ASDs) are a promising plan way to deal with improve the solvency, disintegration rate, and bioavailability of ineffectively water-dissolvable medications. ASDs have confounded physicochemical properties because of the different plans and procedures used to deliver them. These properties impact their physical steadiness, so it is critical to create far reaching and successful portrayal strategies for ASDs. Our comprehension of the properties of ASDs can be improved using a mix of these methods. Key factors that influence the properties of ASDs incorporate the glass change temperature (Tg), atomic portability, miscibility, and crystallinity. The indistinct strong state offers an improved clear dissolvability and disintegration rate. In any case, because of thermodynamic flimsiness and recrystallization inclinations during preparing, stockpiling and disintegration, their potential application is restricted. Therefore, the creation of undefined medications with satisfactory dependability stays a significant test and detailing methodologies dependent on strong atomic scatterings are being abused. Co-indistinct frameworks are another plan approach where the shapeless medication is balanced out through solid intermolecular communications by a low sub-atomic co-previous.

This survey covers a few themes pertinent to co-nebulous medication conveyance frameworks. Specifically, it portrays late advances in the co-nebulous structure, planning and strong state portrayal, just as upgrades of disintegration execution and retention are nitty gritty. Instances of medication tranquilize, sedate carboxylic corrosive and medication amino corrosive co-nebulous scatterings cooperating by means of hydrogen holding, π−π collaborations and ionic powers, are given together comparing last dose structures.

Fruitful improvement of shapeless strong scattering definitions relies upon three essential elements: dynamic pharmaceutical fixing properties, settling polymer, and the preparing innovation. Polymer gives the central structure to settling the nebulous structure and the procedure supplies the vitality required to change the framework into a shapeless structure. This is apparent from plentiful models where just physical blending of the shapeless medication and polymer didn't give agreeable result as far as either improving the solvency or upgrading the bioavailability. Viability of the procedure is basic to produce, catch, and protect the nebulous structure. The accomplishment of these procedures is reliant on the procedure time and the super immersion conditions that are being produced during the arrangement of the strong scattering. From the disclosure of strong scatterings in the mid 1960s, the utilization of strong scattering idea to fathom solvency challenges in certifiable was restricted and this was somewhat because of the absence of industrially suitable preparing innovations.

Be that as it may, in the previous two decades this territory has seen astounding improvement as the science and comprehension of the assembling advances, explicitly splash drying and dissolve expulsion, have advanced significantly prompting a few monetarily fruitful formless items notwithstanding various being developed. Other than propelling the field and logical understanding, numerous innovation driven organizations have flourished in this condition by empowering the improvement of inadequately water-dissolvable medications that would have in any case been dropped from thought. Shower drying and hot-dissolve expulsion have become the foundation of undefined plans in the pharmaceutical business while more current advances are continually being added to the tool compartment that guarantee to improve quality, profitability, as well as better execution of the items. Approaching numerous advancements immensely builds the likelihood of accomplishment for a huge assortment of mixes. The decision of innovation is essentially administered by the physicochemical properties of the medication substance, accessibility of innovation from lab scale to business scale, vigor of the procedure, item execution, and in conclusion the effect of the chose innovation on the expense of products. Investigating the ideal structure space during early period of plan improvement by this methodology requires noteworthy measure of assets including API which might be limitedly accessible during this stage.

Methodology & Theoretical Orientation:

PC-SAFT は、定量的相互作用液体理論 (SAFT) に基づく製剤です。他の SAFT 製剤と同様に、物理化学的手法 (特に粘弾性理論) を使用します。ただし、比較液体として非結合環状粒子を使用する以前の SAFT 製剤とは異なり、比較液体としてハードチェーンの環状粒子を使用します。API 節約手法として、新しい実験モデルと包括的な熱力学的摂動鎖統計的会合流体理論 (PC-SAFT) を使用して、いくつかの製剤の ASD 段階チャートを作成し、構造空間を効率的かつ迅速に調査して、製剤開発を改善しました。これらには、モデル予測結果をテストするために、ICH 条件下での製剤の HME 製造および長期安全性試験 (最大 1 年半) が含まれました。試験では、Soluplus、コポビドン、PVP、HPMCAS などのいくつかの API とポリマー賦形剤が使用されました。

調査結果:

実証装置は、宝石を含まない ASD プランを作成するために必要な排出温度を評価するだけでなく、さまざまな保管条件 (温度と相対湿度) での物理的信頼性を予測するのに完全に適していると判断されました。

結論と意義:

予測可能な ASD レベルチャートの継続的な進歩により、賦形剤の選択、HME 温度予測、および最大薬物負荷と物理的安全性のための ASD データの計画のための強力なツールが実現しています。これらのツールを適用することで、より少ないリソースと材料を使用して、効果的な ASD 定義の合理化が可能になります。