AAPS PharmSciTech最新文献_第8页

Novel Sustained Release Azithromycin Resinate Fabricated by One-Pot Ion-exchange Performed in Hydro-alcoholic Solution 在水醇溶液中通过一锅离子交换法制造出新型缓释阿奇霉素树脂酸盐

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-09-26 DOI: 10.1208/s12249-024-02947-y

Hongyu Liang, Meihui Zhao, Shaoning Wang, Da Wang, Jingxin Gou, Yanjie Bai, Mingyue Shen, Junfeng Wang, Yujie Cheng, Ning Ge, Yi Zhao, Jie Zeng, Lu Sun, Hui Xu

{"title":"Novel Sustained Release Azithromycin Resinate Fabricated by One-Pot Ion-exchange Performed in Hydro-alcoholic Solution","authors":"Hongyu Liang, Meihui Zhao, Shaoning Wang, Da Wang, Jingxin Gou, Yanjie Bai, Mingyue Shen, Junfeng Wang, Yujie Cheng, Ning Ge, Yi Zhao, Jie Zeng, Lu Sun, Hui Xu","doi":"10.1208/s12249-024-02947-y","DOIUrl":"10.1208/s12249-024-02947-y","url":null,"abstract":"<div><p>Drug-resin complexes usually form in the aqueous phase. For poorly water-soluble drugs, low drug loading limits the use of resin in drug formulation. In this study, we used a new method to prepare azithromycin resinates, improving the drug loading rate, shortening the preparation time and simplifying the process. We used hydro-alcoholic solution as the drug loading solvent and the ion exchange resin as the carrier, and this method enabled the resin to adsorb both the retardant and the drug. The sustained release effect of retardant Eudragit RL, RS100 was analyzed. Drug loading efficiency, release profiles, morphology, physicochemical characterization and pharmacokinetic study were assessed. Preparation of drug resinate by batch method resulted in 14% higher drug loading of azithromycin and 3.5 h shorter loading time as compared to pure water for hydroalcoholic solution as drug loading solvent. Raman mappings demonstrated that the retardant with higher molecular weight was more likely to adsorb to the outer layer of the resin compared to the drug. The <i>in vitro</i> release and <i>in vivo</i> pharmacokinetic study of azithromycin resinates showed a sustained release profile with few gastrointestinal adverse effects. Therefore, the addition of ethanol not only improved the efficiency of drug loading but also showed sustained-release effect with one-pot preparation of azithromycin resinates.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigation of Mirabegron-loaded Nanostructured Lipid Carriers for Improved Bioabsorption: Formulation, Statistical Optimization, and In-Vivo Evaluation 用于改善生物吸收的米拉贝琼纳米结构脂质载体的研究：配方、统计优化和体内评估

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-09-25 DOI: 10.1208/s12249-024-02944-1

Pranav Shah, Mansi Patel, Yashwini Kansara, Bhavin Vyas, Pintu Prajapati, Madhulika Pradhan, Sanyog Jain

{"title":"Investigation of Mirabegron-loaded Nanostructured Lipid Carriers for Improved Bioabsorption: Formulation, Statistical Optimization, and In-Vivo Evaluation","authors":"Pranav Shah, Mansi Patel, Yashwini Kansara, Bhavin Vyas, Pintu Prajapati, Madhulika Pradhan, Sanyog Jain","doi":"10.1208/s12249-024-02944-1","DOIUrl":"10.1208/s12249-024-02944-1","url":null,"abstract":"<div><p>Overactive bladder (OAB) is a usual medical syndrome that affects the bladder, and Mirabegron (MBG) is preferred medicine for its control. Currently, available marketed formulations (MYRBETRIQ® granules and MYRBETRIQ® ER tablets) suffer from low bioavailability (29–35%) hampering their therapeutic effectiveness and compromising patient compliance. By creating MBG nanostructured lipid carriers (MBG-NLCs) for improved systemic availability and drug release, specifically in oral administration of OAB treatment, this study aimed to address these issues. MBG-NLCs were fabricated using a hot-melt ultrasonication technique. MBG-GMS; MBG-oleic acid interaction was assessed by in silico molecular docking. QbD relied on the concentration of Span 80 (X1) and homogenizer speed (X2) as critical material attribute (CMA) and critical process parameter (CPP) respectively, while critical quality attributes (CQA) such as particle size (Y1) and cumulative drug release at 24 h (Y2) were estimated as dependent variables. 32 factorial design was utilized to investigate the interconnection in variables that are dependent and independents. Optimized MBG-NLCs with a particle size of 194.4 ± 2.25 nm were suitable for lymphatic uptake. A PDI score of 0.275 ± 0.02 and zeta potential of -36.2 ± 0.721 mV indicated a uniform monodisperse system with stable dispersion properties. MBG-NLCs exhibited entrapment efficiency of 77.3 ± 1.17% and a sustained release in SIF of 94.75 ± 1.60% for 24 h. MBG-NLCs exhibited the Higuchi model with diffusion as a release mechanism. A pharmacokinetic study in Wistar rats exhibited a 1.67-fold higher bioavailability as compared to MBG suspension. Hence, MBG-NLCs hold promise for treating OAB by improving MBG’s oral bio absorption.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a Temperature and pH Dual-Sensitive In-Situ Gel for Treating Allergic Conjunctivitis 开发治疗过敏性结膜炎的温度和酸碱度双敏感原位凝胶

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-09-25 DOI: 10.1208/s12249-024-02931-6

Yanpeng Zhu, Yinghui Liu, Yongyue Wang, Tingting Chen, Xuerui Ma, Ji Li, Dongkai Wang

{"title":"Development of a Temperature and pH Dual-Sensitive In-Situ Gel for Treating Allergic Conjunctivitis","authors":"Yanpeng Zhu, Yinghui Liu, Yongyue Wang, Tingting Chen, Xuerui Ma, Ji Li, Dongkai Wang","doi":"10.1208/s12249-024-02931-6","DOIUrl":"10.1208/s12249-024-02931-6","url":null,"abstract":"<div><p>The purpose of this study was to improve the efficacy of olopatadine hydrochloride (OT) in treating allergic conjunctivitis (AC). To achieve this goal, we developed an eye formulation without antimicrobial agents using a temperature-pH dual-sensitive <i>in situ</i> gel technology combined with heat sterilization. Various types of carbomers were evaluated and their optimal doses determined. The prescription containing poloxamer 407 (P407) and poloxamer 188 (P188) was optimized using central composite design for response surface methodology (CCD-RSM). The final optimized dual-sensitive <i>in situ</i> gel (TP-gel) consisted of 0.1% olopatadine hydrochloride, 18.80% P407, 0.40% P188, 0.30% Pemulen™TR-1(TR-1), 4.0% mannitol, and 0.08% Tri(hydroxymethyl)aminomethane(Tris).Sterilization was performed at a temperature of 121℃ for a duration of 20 min. Experimental results showed that TP-gel had good safety profile and remained on the ocular surface for approximately (65.83 ± 8.79) minutes, which is four times longer than eye drops. The expression levels of IL-13, IL-17, and OVA-IgE in mouse ocular tissues with allergic conjunctivitis treated with TP-gel were significantly reduced. This suggests that TP-gel has the potential to be an effective treatment method for allergic conjunctivitis.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of Sinomenine Hydrochloride Sustained-release Pellet With Multiple Release Characteristics 开发具有多重释放特性的盐酸西诺明缓释颗粒。

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-09-25 DOI: 10.1208/s12249-024-02949-w

Sijun Wu, Guoming Zhou, Xi Wang, Xiaoyang Zhang, Shubo Guo, Yongqiang Ma, Hai Liu, Wenlong Li

{"title":"Development of Sinomenine Hydrochloride Sustained-release Pellet With Multiple Release Characteristics","authors":"Sijun Wu, Guoming Zhou, Xi Wang, Xiaoyang Zhang, Shubo Guo, Yongqiang Ma, Hai Liu, Wenlong Li","doi":"10.1208/s12249-024-02949-w","DOIUrl":"10.1208/s12249-024-02949-w","url":null,"abstract":"<div><p>Due to the gastrointestinal side effects, the clinical application of sinomenine hydrochloride (SH) in rheumatoid arthritis is limited. The elderly population constitutes the primary group affected by this disease, and within this demographic, there are significant variations in gastric emptying time. To reduce the influence of individual differences on drug efficacy and concurrently alleviate gastrointestinal side effects, the SH sustained-release pellets with multiple release characteristics were developed, which comprised both regular sustained-release pellets and enteric-coated sustained-release pellets. The drug-loaded layer formulation was optimized by full factorial design. With the optimal formulation, the drug-loaded pellets achieved a yield of 96.05%, an encapsulation efficiency of 83.36% for SH, a relative standard deviation of 3.26% in SH content distribution, an average roundness of 0.971 for the pellets, and the particle size span of 0.808. The pellets with a 4 h SH release profile in an acidic environment and pellets displaying 4 h acid resistance followed by an 8 h SH release behavior in the intestinal environment were individually prepared through <i>in vitro</i> dissolution tests. The results demonstrated stable and compliant dissolution behavior of the formulation, along with excellent stability and physical appearance. This research offers novel insights and references for the innovative formulation of SH.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and Characterization of Olaparib-Loaded Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Pharmaceutical Applications 用于制药的奥拉帕里布负载型固体自纳米乳化给药系统（S-SNEDDS）的开发与表征。

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-09-24 DOI: 10.1208/s12249-024-02927-2

Yuseon Shin, Mikyung Kim, Chaeyeon Kim, Hyewon Jeon, Jain Koo, Jimin Oh, Soyoung Shin, Yu Seok Youn, Chaemin Lim, Kyung Taek Oh

{"title":"Development and Characterization of Olaparib-Loaded Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Pharmaceutical Applications","authors":"Yuseon Shin, Mikyung Kim, Chaeyeon Kim, Hyewon Jeon, Jain Koo, Jimin Oh, Soyoung Shin, Yu Seok Youn, Chaemin Lim, Kyung Taek Oh","doi":"10.1208/s12249-024-02927-2","DOIUrl":"10.1208/s12249-024-02927-2","url":null,"abstract":"<div><p>This study aims to enhance the solubility of Olaparib, classified as biopharmaceutical classification system (BCS) class IV due to its low solubility and bioavailability using a solid self-nanoemulsifying drug delivery system (S-SNEDDS). For this purpose, SNEDDS formulations were created using Capmul MCM as the oil, Tween 80 as the surfactant, and PEG 400 as the co-surfactant. The SNEDDS formulation containing olaparib (OLS-352), selected as the optimal formulation, showed a mean droplet size of 87.0 ± 0.4 nm and drug content of 5.53 ± 0.09%. OLS-352 also demonstrated anticancer activity against commonly studied ovarian (SK-OV-3) and breast (MCF-7) cancer cell lines. Aerosil® 200 and polyvinylpyrrolidone (PVP) K30 were selected as solid carriers, and S-SNEDDS formulations were prepared using the spray drying method. The drug concentration in S-SNEDDS showed no significant changes (98.4 ± 0.30%, 25℃) with temperature fluctuations during the 4-week period, demonstrating improved storage stability compared to liquid SNEDDS (L-SNEDDS). Dissolution tests under simulated gastric and intestinal conditions revealed enhanced drug release profiles compared to those of the raw drug. Additionally, the S-SNEDDS formulation showed a fourfold greater absorption in the Caco-2 assay than the raw drug, suggesting that S-SNEDDS could improve the oral bioavailability of poorly soluble drugs like olaparib, thus enhancing therapeutic outcomes. Furthermore, this study holds significance in crafting a potent and cost-effective pharmaceutical formulation tailored for the oral delivery of poorly soluble drugs.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Surface Solid Dispersion of Ketoconazole on Trehalose Dihydrate using Spray Drying to Achieve Enhanced Dissolution Rate 利用喷雾干燥法将酮康唑表面固体分散在二水曲哈洛糖上以提高溶解率

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-09-23 DOI: 10.1208/s12249-024-02941-4

Wanlop Weecharangsan, Robert J. Lee

{"title":"Surface Solid Dispersion of Ketoconazole on Trehalose Dihydrate using Spray Drying to Achieve Enhanced Dissolution Rate","authors":"Wanlop Weecharangsan, Robert J. Lee","doi":"10.1208/s12249-024-02941-4","DOIUrl":"10.1208/s12249-024-02941-4","url":null,"abstract":"<div><p>Ketoconazole (K) is a poorly water-soluble drug that faces significant challenges in achieving therapeutic efficacy. This study aimed to enhance the dissolution rate of ketoconazole by depositing spray-dried ketoconazole (SK) onto the surface of ground trehalose dihydrate (T) using spray drying. Ketoconazole-trehalose surface solid dispersions (SKTs) were prepared in ratios of 1:1 (SK1T1), 1:4 (SK1T4), and 1:10 (SK1T10), and characterized them using particle size analysis, scanning electron microscopy, powder X-ray diffraction, and <i>in vitro</i> dissolution studies. Results showed that the dissolution rates of the dispersions were significantly higher than those of pure ketoconazole, with the 1:10 ratio showing the highest dissolution rate. The improved dissolution was attributed to the formation of a new crystalline phase and better dispersion of ketoconazole particles. These findings suggest that the surface solid dispersion approach could be a valuable method for enhancing the bioavailability of poorly water-soluble drugs.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Monitoring of Isothermal Crystallization and Time–Temperature Transformation of Amorphous Felodipine: The Time-Domain Nuclear Magnetic Resonance Method 监测无定形非洛地平的等温结晶和时温转变：时域核磁共振法。

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-09-19 DOI: 10.1208/s12249-024-02919-2

A. Pajzderska, M. A. Gonzalez, M. Jarek, J. Wąsicki

引用次数: 0

Development, Pharmacokinetics and Antimalarial Evaluation of Dose Flexible 3D Printlets of Dapsone for Pediatric Patients 用于儿科患者的剂量灵活的 3D打印小剂量达哌酮的开发、药代动力学和抗疟评估

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-09-17 DOI: 10.1208/s12249-024-02935-2

Adnan A. Khan, Tahir Khuroo, Eman M Mohamed, Sathish Dharani, Kayalar Canberk, Xiaoyu Zhang, Lamba Omar Sangaré, Mathew A. Kuttolamadom, Allison C. Rice-Ficht, Ziyaur Rahman

{"title":"Development, Pharmacokinetics and Antimalarial Evaluation of Dose Flexible 3D Printlets of Dapsone for Pediatric Patients","authors":"Adnan A. Khan, Tahir Khuroo, Eman M Mohamed, Sathish Dharani, Kayalar Canberk, Xiaoyu Zhang, Lamba Omar Sangaré, Mathew A. Kuttolamadom, Allison C. Rice-Ficht, Ziyaur Rahman","doi":"10.1208/s12249-024-02935-2","DOIUrl":"10.1208/s12249-024-02935-2","url":null,"abstract":"<p>The focus of current studies was to fabricate dose flexible printlets of dapsone (DDS) for pediatric patients by selective laser sintering (SLS) 3D printing method, and evaluate its physicochemical, patient in-use stability, and pharmacokinetic attributes. Eight formulations were fabricated using Kollicoat<sup>®</sup> IR, Eudragit<sup>®</sup> L-100-55 and StarCap<sup>®</sup>as excipients and evaluated for hardness, disintegration, dissolution, amorphous phase by differential scanning calorimetry and X-ray powder diffraction, in-use stability at 30 <sup>o</sup>C/75% RH for a month, and pharmacokinetic study in Sprague Dawley rats. The hardness, and disintegration of the printlets varied from 2.6±1.0 (F4) to 7.7±0.9 (F3) N and 2.0±0.4 (F2) to 7.6±0.6 (F3) sec, respectively. The drug was partially present as an amorphous form in the printlets. The drug was completely (>85%) dissolved in 20 min. No change in drug form or dissolution extent was observed after storage at in use condition. Pharmacokinetic profiles of both formulations (tablets and printlets) were almost superimposable with no statistical difference in pharmacokinetic parameters (T<sub>max</sub>, C<sub>max</sub>, and AUC<sub>0-</sub><sub>¥</sub>)between formulations (p>0.05). Values of EC<sub>50</sub> (half maximal effective concentration) and EC<sub>90</sub> (maximal concentration inducing 90% maximal response) were 0.50±0.15 and 1.32±0.26 mM, 0.41±0.06 and 1.11±0.21, and 0.42±0.13 and 1.36±0.19 mM for DDS, printlet and tablet formulations, respectively, and differences were statistically insignificant (p>0.05). In conclusion, tablet and printlet formulations are expected to be clinical similar, thus clinically interchangeable.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PEGylated pH-Responsive Liposomes for Enhancing the Intracellular Uptake and Cytotoxicity of Paclitaxel in MCF-7 Breast Cancer Cells 用于增强 MCF-7 乳腺癌细胞对紫杉醇的胞内吸收和细胞毒性的 PEG 化 pH 响应脂质体

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-09-17 DOI: 10.1208/s12249-024-02930-7

Harsh P. Nijhawan, Pooja Shyamsundar, Bala Prabhakar, Khushwant S. Yadav

{"title":"PEGylated pH-Responsive Liposomes for Enhancing the Intracellular Uptake and Cytotoxicity of Paclitaxel in MCF-7 Breast Cancer Cells","authors":"Harsh P. Nijhawan, Pooja Shyamsundar, Bala Prabhakar, Khushwant S. Yadav","doi":"10.1208/s12249-024-02930-7","DOIUrl":"10.1208/s12249-024-02930-7","url":null,"abstract":"<div><p>This study aimed to develop paclitaxel (PTX)-loaded PEGylated (PEG)-pH-sensitive (SpH) liposomes to enhance drug delivery efficiency and cytotoxicity against MCF-7 breast cancer cells. PTX-loaded PEG-SpH liposomes were prepared using the thin film hydration method. ATR-FTIR compatibility studies revealed no significant interactions among liposome formulation components. TEM images confirmed spherical morphology, stability, and an ideal size range (180–200 nm) for improved blood circulation. At pH 5.5, liposomes exhibited increased size and positive zeta potential, indicating pH-sensitive properties due to CHEMS response to the acidic tumor microenvironment. Conversely, at pH 7.4, liposomes showed a slightly larger size (199.25 ± 1.64 nm) and a more negative zeta potential (-36.94 ± 0.32 mV), suggesting successful PEG-SpH surface modification, enhancing stability, and reducing aggregation. PTX-loaded PEG-SpH liposomes demonstrated high encapsulation efficiency (84.57 ± 0.92% w/w) and drug loading capacity (4.12 ± 0.26% w/w). <i>In-vitro</i> drug release studies revealed accelerated first-order PTX release at pH 5.5 and a controlled zero-order release at pH 7.4. Cellular uptake studies on MCF-7 cells demonstrated enhanced PTX uptake, attributed to mPEG-PCL incorporation prolonging circulation time and CHEMS facilitating PTX release in the tumor microenvironment. Furthermore, PTX-loaded PEG-SpH liposomes exhibited significantly improved cytotoxicity with an IC<sub>50</sub> value of 1.107 µM after 72-h incubation, approximately 90% lower than plain PTX solution. Stability studies confirmed the robustness of the liposomal formulation under various storage conditions. These findings highlight the potential of PEGylated pH-responsive liposomes as effective nanocarriers for enhancing PTX therapy against breast cancer.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preparation and In Vitro Evaluation of Montelukast Sodium-Loaded 3D Printed Orodispersible Films for the Treatment of Asthma 用于治疗哮喘的负载孟鲁司特钠三维打印可分散薄膜的制备和体外评估

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-09-17 DOI: 10.1208/s12249-024-02938-z

Ece Özcan-Bülbül, Yağmur Kalender, Ayça Bal-Öztürk, Neslihan Üstündağ-Okur

{"title":"Preparation and In Vitro Evaluation of Montelukast Sodium-Loaded 3D Printed Orodispersible Films for the Treatment of Asthma","authors":"Ece Özcan-Bülbül, Yağmur Kalender, Ayça Bal-Öztürk, Neslihan Üstündağ-Okur","doi":"10.1208/s12249-024-02938-z","DOIUrl":"10.1208/s12249-024-02938-z","url":null,"abstract":"<div><p>This research aims to produce orodispersible films (ODFs) and determine their potential use in the oral delivery of montelukast sodium for asthma treatment and allergic rhinitis. ODFs were successfully developed by Three-dimensional (3D) printing using propylene glycol (PG), and hydroxypropyl methylcellulose (HPMC), polyethylene glycol 400 (PEG). Finally, the amount of montelukast sodium in the ODFs was 5% (w/w). Drug-excipients compatibility with Fourier Transformed Infrared (FTIR) spectroscopy, mass uniformity, thickness, disintegration time, folding endurance, moisture absorption, pH, <i>in vitro</i> drug release (dissolution), drug content, moisture loss, moisture content, mechanical properties, and cytotoxicity studies were performed on the prepared films. All formulations disintegrated in approximately 40 s. Over 98% of drug release from all films within 2 min was confirmed. It was reported that Fm1-4 (8% HPMC and 1% PEG) and Fm2-4 (10% HPMC and 3% PEG) are more suitable for drug content, but Fm2-4 may be the ideal formulation considering its durability and transportability properties. Based on the characterization results and <i>in vitro</i> release values, the montelukast sodium ODF can be an option for other dosage forms. It was concluded that the formulations did not show toxic potential by <i>in vitro</i> cytotoxicity study with 3T3 cells. This new formulation can efficiently treat allergic rhinitis and asthma diseases.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0