長期作用の筋内ヴォルティオキセチンパモアートサスペンションの開発:製剤の最適化と薬物動態評価
Yanhui Li1, Ting Wang1, Menghan Liu2
1CSPC Pharmaceutical Group Co., Ltd., 896 East Zhongshan Road, Shijiazhuang 050035, PR China; State Key Laboratory of New Pharmaceutical Preparations and Excipients, Shijiazhuang 050035, PR China.
まとめ
この研究では,長時間作用する筋内ヴォルティオキセチンパモアート (VTXP) サスペンションを開発しました. 最適化された2.5μmのVTXPサスペンションは,動物モデルで薬剤の放出が延長され,低バースト放出が示され,持続的な出産の可能性が確認されました.
科学分野:
- 医薬品科学 医薬品科学とは
- 薬物の配送システムです.
- ファルマコキネティクス
背景:
- ヴォルティオキセチンは抗うつ薬であり,患者の従順性を高めるために改善された長期作用の配方が必要です.
- 筋内投与 (IM) の薬剤投与は,持続的な放出の可能性がありますが,課題には,配方安定性と注射特性があります.
研究 の 目的:
- 長時間作用する筋内ヴォルティオキセチンパモアート (VTXP) サスペンションの開発と特徴付け.
- 最適化されたVTXPサスペンションの薬理学プロファイルとインビヴォ性能を評価する.
主な方法:
- VTXPのサスペンションは,惑星球磨き機を使用して準備され,ポロキサマー338.8で安定化されました.
- 特徴付けには,粒子の大きさ分析 (レーザー difraktion),粘度,注入力,固体分析 (XRPD),およびin vitro放出研究が含まれていました.
- ラットと犬で実施された薬物動態 (PK) 研究では,IMと胃内 (IG) 投与を比較した.
主要な成果:
- 3%ポロキサマー338を含む15%の最適化されたVTXPサスペンションは,適切な粘度と注射力を示した.
- 2.5μmのVTXPサスペンションは,ラットと犬のIG投与と比較して,IM投与による半減期 (t1/2) を大幅に延長した.
- IMで投与されたサスペンションでは,バストリリースの割合が低かった (ネズミ10.2%,犬3.8%).
結論:
- 開発されたVTXPサスペンション製剤は,長時間作用の筋肉内投与に適しています.
- 2.5μmの粒子のサイズのサスペンションは,持続的な薬剤の放出と,バーストの放出を減らすことを実証し,長期的な作用の有望な配送オプションを提供しています.
関連する概念動画
01:05Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
238
Body:Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
238
01:27Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
197
Changes in polymorphic forms can significantly influence the bioavailability of poorly soluble drugs. Although the FDA defines pharmaceutical equivalence based on having the same active ingredient, dosage form, and route of administration, it does not automatically disqualify products with different polymorphic forms. This means two products with different polymorphs can still be deemed pharmaceutically equivalent. However, polymorphic differences can affect properties like wettability,...
197
01:30Modified-Release Drug Delivery Systems: Bioavailability
31
Modified-release (MR) dosage forms are designed to extend drug release over time, thereby maintaining stable plasma concentrations and reducing dosing frequency. However, their bioavailability is typically below 100% due to incomplete drug release and presystemic metabolism, and limitations in drug permeability across the gastrointestinal epithelium, all of which can restrict the fraction of the drug reaching systemic circulation. Consequently, studying the in vivo bioavailability of MR...
31
01:17In Vitro Drug Dissolution: Alternative Methods
271
Alternative drug dissolution methods include the rotating bottle, intrinsic dissolution test, peristalsis, and the Franz diffusion cell method. The rotating bottle method involves meticulously rotating tightly capped controlled-release beads in a temperature-controlled bath. Periodic decanting of samples allows for residue assay, followed by refilling with fresh medium and testing at various pH levels to emulate the gastrointestinal tract conditions.In contrast, the intrinsic dissolution test...
271
01:22Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence
221
Generic intravenous (IV) drugs are considered bioequivalent to their branded counterparts due to their 100% bioavailability upon administration. However, variations in stability among different drug products can significantly influence their therapeutic performance, even if they are pharmaceutically equivalent.Cefuroxime, a prophylactic antimicrobial, is often used as a single-dose IV injection for patients undergoing coronary artery bypass grafting surgery. A 3 g dose typically provides...
221
01:28Factors Influencing Drug Absorption: Pharmaceutical Parameters
652
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
652