AAPS PharmSciTech最新文献_第5页

In Situ Forming Hydrogel Reinforced with Antibiotic-Loaded Mesoporous Silica Nanoparticles for the Treatment of Bacterial Keratitis 用抗生素负载介孔二氧化硅纳米粒子增强的原位形成水凝胶用于治疗细菌性角膜炎

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-10-23 DOI: 10.1208/s12249-024-02969-6

Mohammad Mohammadi, Shokoufeh Rahmani, Zohre Ebrahimi, Ghazal Nowroozi, Fatemeh Mahmoudi, Mohsen Shahlaei, Sajad Moradi

{"title":"In Situ Forming Hydrogel Reinforced with Antibiotic-Loaded Mesoporous Silica Nanoparticles for the Treatment of Bacterial Keratitis","authors":"Mohammad Mohammadi, Shokoufeh Rahmani, Zohre Ebrahimi, Ghazal Nowroozi, Fatemeh Mahmoudi, Mohsen Shahlaei, Sajad Moradi","doi":"10.1208/s12249-024-02969-6","DOIUrl":"10.1208/s12249-024-02969-6","url":null,"abstract":"<div><p>Bacterial keratitis (BK) is a serious ocular infection that can lead to vision impairment or blindness if not treated promptly. Herein, we report the development of a versatile composite hydrogel consisting of silk fibroin and sodium alginate, reinforced by antibiotic-loaded mesoporous silica nanoparticles (MSNs) for the treatment of BK. The drug delivery system is constructed by incorporating vancomycin- and ceftazidime-loaded MSNs into the hydrogel network. The synthesized MSNs were found to be spherical in shape with an average size of about 95 nm. The loading capacities of both drugs were approximately 45% and 43%, for vancomycin and ceftazidime respectively. Moreover, the formulation exhibited a sustained release profile, with 92% of vancomycin and 90% of ceftazidime released over a 24 h period. The cytocompatibility of the drug carrier was also confirmed by MTT assay results. In addition, we performed molecular dynamics (MD) simulations to better reflect the drug-drug and drug-MSN interactions. The results obtained from RMSD, number of contacts, and MSD analyses perfectly corroborated the experimental findings. In brief, the designed drug-MSN@hydrogel could mark an intriguing new chapter in the treatment of BK.</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 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492631","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 Minodronic Acid-Loaded Dissolving Microneedles for Enhanced Osteoporosis Therapy: Influence of Drug Loading on the Bioavailability of Minodronic Acid 开发用于骨质疏松症强化治疗的米诺膦酸负载溶解微针：药物负载对米诺膦酸生物利用率的影响。

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-10-23 DOI: 10.1208/s12249-024-02963-y

Beibei Yang, Zeshi Jiang, Xiaoqian Feng, Jingxin Yang, Chao Lu, Chuanbin Wu, Xin Pan, Tingting Peng

{"title":"Development of Minodronic Acid-Loaded Dissolving Microneedles for Enhanced Osteoporosis Therapy: Influence of Drug Loading on the Bioavailability of Minodronic Acid","authors":"Beibei Yang, Zeshi Jiang, Xiaoqian Feng, Jingxin Yang, Chao Lu, Chuanbin Wu, Xin Pan, Tingting Peng","doi":"10.1208/s12249-024-02963-y","DOIUrl":"10.1208/s12249-024-02963-y","url":null,"abstract":"<div><p>Osteoporosis is a metabolic bone disorder with impaired bone microstructure and increased bone fractures, seriously affecting the quality of life of patients. Among various bisphosphonates prescribed for managing osteoporosis, minodronic acid (MA) is the most potent inhibitor of bone context resorption. However, oral MA tablet is the only commercialized dosage form that has extremely low bioavailability, severe adverse reactions, and poor patient compliance. To tackle these issues, we developed MA-loaded dissolving microneedles (MA-MNs) with significantly improved bioavailability for osteoporosis therapy. We investigated the influence of drug loading on the physicochemical properties, transdermal permeation behavior, and pharmacokinetics of MA-MNs. The drug loading of MA-MNs exerted almost no effect on their morphology, mechanical property, and skin insertion ability, but it compromised the transdermal permeability and bioavailability of MA-MNs. Compared with oral MA, MA-MNs with the lowest drug loading (224.9 μg/patch) showed a 9-fold and 25.8-fold increase in peak concentration and bioavailability, respectively. This may be ascribed to the reason that the increased drug loading can generate higher burst release, higher drug residual rate, and drug supersaturation effect in skin tissues, eventually limiting drug absorption into the systemic circulation. Moreover, MA-MNs prolonged the half-life of MA and provided more steady plasma drug concentrations than intravenously injected MA, which helps to reduce dosing frequency and side effects. Therefore, dissolving MNs with optimized drug loading provides a promising alternative for bisphosphonate drug delivery.</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 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492629","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 Predictive Statistical Model for Gaining Valuable Insights in Pharmaceutical Product Recalls 开发预测性统计模型，为药品召回提供有价值的见解。

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-10-23 DOI: 10.1208/s12249-024-02970-z

Jayshil A. Bhatt, Kenneth R. Morris, Rahul V. Haware

{"title":"Development of Predictive Statistical Model for Gaining Valuable Insights in Pharmaceutical Product Recalls","authors":"Jayshil A. Bhatt, Kenneth R. Morris, Rahul V. Haware","doi":"10.1208/s12249-024-02970-z","DOIUrl":"10.1208/s12249-024-02970-z","url":null,"abstract":"<div><p>The rapid progress in artificial intelligence (AI) has revolutionized problem-solving across various domains. The global challenge of pharmaceutical product recalls imposes the development of effective tools to control and reduce shortage of pharmaceutical products and help avoid such recalls. This study employs AI, specifically machine learning (MI), to analyze critical factors influencing formulation, manufacturing, and formulation complexity which could offer promising avenue for optimizing drug development processes. Utilizing FDAZilla and SafeRX tools, an open database model was constructed, and predictive statistical models were developed using Multivariate Analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) Approach. The study focuses on key descriptors such as delivery route, dosage form, dose, BCS classification, solid-state and physicochemical properties, release type, half-life, and manufacturing complexity. Through statistical analysis, a data simplification process identifies critical descriptors, assigning risk numbers and computing a cumulative risk number to assess product complexity and recall likelihood. Partial Least Square Regression and the LASSO approach established quantitative relationships between key descriptors and cumulative risk numbers. Results have identified key descriptors; BCS Class I, dose number, release profile, and drug half-life influencing product recall risk. The LASSO model further confirms these identified descriptors with 71% accuracy. In conclusion, the study presents a holistic AI and machine learning approach for evaluating and forecasting pharmaceutical product recalls, underscoring the importance of descriptors, formulation complexity, and manufacturing processes in mitigating risks associated with product quality.\u0000</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 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492630","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

Understanding of Wetting Mechanism Toward the Sticky Powder and Machine Learning in Predicting Granule Size Distribution Under High Shear Wet Granulation 了解粘性粉末的润湿机制和机器学习在预测高剪切湿法制粒过程中的粒度分布。

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-10-23 DOI: 10.1208/s12249-024-02973-w

Yanling Jiang, Kangming Zhou, Huai He, Yu Zhou, Jincao Tang, Tianbing Guan, Shuangkou Chen, Taigang Zhou, Yong Tang, Aiping Wang, Haijun Huang, Chuanyun Dai

{"title":"Understanding of Wetting Mechanism Toward the Sticky Powder and Machine Learning in Predicting Granule Size Distribution Under High Shear Wet Granulation","authors":"Yanling Jiang, Kangming Zhou, Huai He, Yu Zhou, Jincao Tang, Tianbing Guan, Shuangkou Chen, Taigang Zhou, Yong Tang, Aiping Wang, Haijun Huang, Chuanyun Dai","doi":"10.1208/s12249-024-02973-w","DOIUrl":"10.1208/s12249-024-02973-w","url":null,"abstract":"<div><p>The granulation of traditional Chinese medicine (TCM) has attracted widespread attention, there is limited research on the high shear wet granulation (HSWG) and wetting mechanisms of sticky TCM powders, which profoundly impact the granule size distribution (GSD). Here we investigate the wetting mechanism of binders and the influence of various parameters on the GSD of HSWG and establish a GSD prediction model. Permeability and contact angle experiments combined with molecular dynamics (MD) simulations were used to explore the wetting mechanism of hydroalcoholic solutions with TCM powder. Machine learning (ML) was employed to build a GSD prediction model, feature importance explained the influence of features on the predictive performance of the model, and correlation analysis was used to assess the influence of various parameters on GSD. The results show that water increases powder viscosity, forming high-viscosity aggregates, while ethanol primarily acted as a wetting agent. The contact angle of water on the powder bed was the largest and decreased with an increase in ethanol concentration. Extreme Gradient Boosting (XGBoost) outperformed other models in overall prediction accuracy in GSD prediction, the binder had the greatest impact on the predictions and GSD, adjusting the amount and concentration of adhesive can control the adhesion and growth of granules while the impeller speed had the least influence on granulation. The study elucidates the wetting mechanism and provides a GSD prediction model, along with the impact of material properties, formulation, and process parameters obtained, aiding the intelligent manufacturing and formulation development of TMC.</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 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492632","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

Effects of Glass Bead Size on Dissolution Profiles in Flow-through Dissolution Systems (USP 4) 玻璃珠尺寸对流动溶解系统溶解曲线的影响 (USP 4)

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-10-22 DOI: 10.1208/s12249-024-02972-x

Hiroyuki Yoshida, Keita Teruya, Yasuhiro Abe, Takayuki Furuishi, Kaori Fukuzawa, Etsuo Yonemochi, Ken-ichi Izutsu

{"title":"Effects of Glass Bead Size on Dissolution Profiles in Flow-through Dissolution Systems (USP 4)","authors":"Hiroyuki Yoshida, Keita Teruya, Yasuhiro Abe, Takayuki Furuishi, Kaori Fukuzawa, Etsuo Yonemochi, Ken-ichi Izutsu","doi":"10.1208/s12249-024-02972-x","DOIUrl":"10.1208/s12249-024-02972-x","url":null,"abstract":"<div><p>The effects of glass bead size in the conical space of flow-through cells on the dissolution profiles were investigated in a USP apparatus 4. Dissolution tests of disintegrating and non-disintegrating tablets in flow-through dissolution systems were performed using semi-high precision glass beads with diameters ranging from 0.5 mm to 1.5 mm. Computational fluid dynamics (CFD) was used to evaluate the effect of shear stress from the dissolution media flow. The use of smaller glass beads in a larger cell resulted in a faster dissolution of the model formulations under certain test conditions. The effect on the dissolution was highly dependent on the size of the beads in the top layer, including those in contact with the tablets. The absence of a bead-size effect on the dissolution of an orodispersible tablet in a small cell can be explained by the floating fragments during the test. CFD analysis showed that smaller bead diameters led to greater shear stress on the tablet, which was correlated with the dissolution rate. Hence, fluid flow through the narrow gaps between the small beads generated strong local flows, causing shear stress. The size of the glass beads used in flow-through cells affects the dissolution rate of tablets by altering the shear stress on the tablets in certain cases (e.g., direct deposition of the formulation on glass beads, large cells, and very low flow rates). Thus, glass bead size must be considered for a robust dissolution test in a flow-through cell system.</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 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453091","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

Demystifying the Potential of Embelin-Loaded Nanoformulations: a Comprehensive Review 解密栓皮肽载体纳米制剂的潜力：全面综述

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-10-21 DOI: 10.1208/s12249-024-02968-7

Layba Noor, Abdul Hafeez, Md. Azizur Rahman, Km Khushboo Vishwakarma, Archita Kapoor, Nargis Ara, Rabia Aqeel

{"title":"Demystifying the Potential of Embelin-Loaded Nanoformulations: a Comprehensive Review","authors":"Layba Noor, Abdul Hafeez, Md. Azizur Rahman, Km Khushboo Vishwakarma, Archita Kapoor, Nargis Ara, Rabia Aqeel","doi":"10.1208/s12249-024-02968-7","DOIUrl":"10.1208/s12249-024-02968-7","url":null,"abstract":"<div><p>Phytoconstituent based therapies have the potential to reduce the adverse effects and enhance overall patient compliance for different diseased conditions. Embelin (EMB) is a natural compound extracted from <i>Embelia ribes</i> that has demonstrated high therapeutic potential, particularly as anti-inflammatory and anticancer therapeutic applications. However, its poor water solubility and low oral bioavailability limitations make it challenging to use in biomedical applications. Nanostructure-based novel formulations have shown the potential to improve physicochemical and biological characteristics of active pharmaceutical ingredients obtained from plants. Different nanoformulations that have been utilized to encapsulate/entrap EMB for various therapeutic applications are nanoliposomes, nanostructured lipid carriers, niosomes, polymeric nanoparticles, nanosuspensions, phytosomes, self nanoemulsifying drug delivery system, silver nanoparticles, microparticles, solid lipid nanoparticle, gold nanoparticles and nanomicelles. The common methods reported for the preparation of EMB nanoformulations are thin film hydration, nanoprecipitation, ethanol injection, emulsification followed by sonication. The size of nanoformulations ranged in between 50 and 345 nm. In this review, the mentioned EMB loaded nanocarriers are methodically discussed for size, shape, drug entrapment, zeta potential, <i>in vitro</i> release & permeation and <i>in vivo</i> studies. Potential of EMB with other drugs (dual drug approach) incorporated in nanocarriers are also discussed (physicochemical and preclinical characteristics). Patents related to EMB nanoformulations are also presented which showed the clinical translation of this bioactive for future utilization in different indications.</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 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452943","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

Effect of Liquid Load Level and Binder Type on the Tabletability of Mesoporous Silica Based Liquisolids 液体装载量和粘合剂类型对介孔二氧化硅基胶凝剂片剂性的影响

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-10-21 DOI: 10.1208/s12249-024-02958-9

Jan Appelhaus, Kristina E. Steffens, Karl G. Wagner

{"title":"Effect of Liquid Load Level and Binder Type on the Tabletability of Mesoporous Silica Based Liquisolids","authors":"Jan Appelhaus, Kristina E. Steffens, Karl G. Wagner","doi":"10.1208/s12249-024-02958-9","DOIUrl":"10.1208/s12249-024-02958-9","url":null,"abstract":"<div><p>Mesoporous silica offers an easy way to transform liquids into solids, due to their high loading capacity for liquid or dissolved active ingredients and the resulting enhanced dissolution properties. However, the compression of both unloaded and loaded mesoporous silica bulk material into tablets is challenging, due to poor/non-existing binding capacity. This becomes critical when high drug loads are to be achieved and the fraction of additional excipients in the final tablet formulation needs to be kept at a minimum. Our study aimed to investigate the mechanism of compression and tabletability dependent on the Liquid Load Level of the silica and type of filler/binder in binary tabletting mixtures. To this end, Vivapur® 101, FlowLac® 90, Pearlitol® 200 SD and tricalcium citrate tetrahydrate were selected and mixed with Syloid® XDP 3050 at various Liquid Load Levels. Compaction characteristics were analysed using the StylOne® Classic 105 ML compaction simulator. Additionally, the Overall Liquid Load (OLL) was defined as a new critical quality attribute for liquisolid tablets. The Overall Liquid Load allows straightforward, formulation-relevant comparisons between various fillers/binders, liquid components, and silica types. Results indicate strong binding capacity and high plasticity of the fillers/binders as key components for successful high liquid load silica tablet formulation. A volumetric combination of 30% Vivapur® 101 and 70% 0.75 mL/g loaded Syloid® XDP 3050 proved to be the most effective mixture, achieving an Overall Liquid Load of 36–41% [<i>v</i>/<i>v</i>] and maintaining a tensile strength of 1.5 N/mm<sup>2</sup> with various liquid vehicles.</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 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-02958-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Paroxetine Loaded Nanostructured Lipid Carriers Based In-situ Gel for Brain Delivery via Nasal Route for Enhanced Anti-Depressant Effect: In Vitro Prospect and In Vivo Efficacy 基于纳米结构脂质载体的帕罗西汀负载原位凝胶通过鼻腔途径给药大脑以增强抗抑郁效果：体外前景和体内疗效

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-10-21 DOI: 10.1208/s12249-024-02954-z

Kiran Akbar, Masood Ur Rehman, Fawad Ali Shah, Sidra Younas, Jamelah S. Al-Otaibi, Haroon Khan

{"title":"Paroxetine Loaded Nanostructured Lipid Carriers Based In-situ Gel for Brain Delivery via Nasal Route for Enhanced Anti-Depressant Effect: In Vitro Prospect and In Vivo Efficacy","authors":"Kiran Akbar, Masood Ur Rehman, Fawad Ali Shah, Sidra Younas, Jamelah S. Al-Otaibi, Haroon Khan","doi":"10.1208/s12249-024-02954-z","DOIUrl":"10.1208/s12249-024-02954-z","url":null,"abstract":"<div><p>This study focused on developing a thermosensitive gel with nanostructured lipid carriers (NLCs) loaded with paroxetine (PAR) to enhance the treatment and management of depression via nasal administration. Micro emulsion technique was utilized for the PAR-NLCs preparation. The acetyl alcohol and oleic acid were used in the ratio of 76:24. In the NLCs Tween 40, Span40 and Myrj 52 were used as a surfactant. The NLCs were then added into Poloxamer mixture to get thermosensitive NLCs based gel. Characterization, <i>in vitro</i> and <i>in vivo</i> studies were performed to check the efficiency of formulation in drug delivery. The entrapment efficiency of optimized PAR-NLCs was about 90%. The particle size, zeta potential and PDI were 155 ± 1.4 nm, -25.9 ± 0.5 mV, and 0.12 ± 0.01 respectively. The optimized gel showed a gelling temperature of 31.50 ± 0.50°C and a gelling time of 1 ± 0.12 s with a pH of 6, suitable for nasal administration. The <i>in vitro</i> release assay of PAR-NLC-gel showed a cumulative release of about 59% in the first 6 h after comparison with PAR-NLCs which showed almost 100%release. <i>In vivo</i> studies included forced swim test and tail suspension tests showed significant potential for treating depression when compared to PAR-NLCs. PAR-NLCs and NLCs based gel enhanced the tissue architecture and suppressed the expression of TNF-α in brain cortex from histological and immunohistochemical analysis. PAR- NLCs gel-based delivery system can prove to be an effective delivery system for brain targeting through nose for the better management of depression.</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 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453090","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

Systematic Approach in the Development of Chitosan Functionalized Iloperidone Nanoemulsions for Transnasal Delivery, In Vitro and In Vivo Studies 开发用于经鼻给药的壳聚糖功能化伊洛哌酮纳米乳剂的系统方法、体外和体内研究

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-10-21 DOI: 10.1208/s12249-024-02964-x

Niserga D. Sawant, Pratima A. Tatke, Namita D. Desai

{"title":"Systematic Approach in the Development of Chitosan Functionalized Iloperidone Nanoemulsions for Transnasal Delivery, In Vitro and In Vivo Studies","authors":"Niserga D. Sawant, Pratima A. Tatke, Namita D. Desai","doi":"10.1208/s12249-024-02964-x","DOIUrl":"10.1208/s12249-024-02964-x","url":null,"abstract":"<p>Iloperidone, a second-generation USFDA approved antipsychotic and BCS class II drug shows poor oral bioavailability of 28%. The present research deals with optimization of transnasal nanoemulsions of Iloperidone using Design Expert (Version 11) and further surface functionalization with chitosan for potentiating nose to brain delivery. Chitosan functionalized transnasal Iloperidone nanoemulsions were developed using oleic acid, charge inducer, Tween 80, Transcutol HP and chitosan using ultrasonication technique and evaluated. Droplet size, polydispersity index and zeta potential of Iloperidone nanoemulsions was found to be 173 ± 0.5 nm, 0.413 ± 0.2 and − 22.5 ± 0.1 mV while that of chitosan functionalized Iloperidone nanoemulsions was 146.4 ± 0.5 nm, 0.291 ± 0.02 and + 23.6 ± 0.3 mV respectively. Ninhydrin assay, TEM and FTIR studies confirmed surface functionalization of Iloperidone nanoemulsion droplets with chitosan. <i>In vitro</i> release of Iloperidone from nanoemulsions and chitosan functionalized nanoemulsions was 90.41 ± 2.1% and 72.02 ± 0.21% while <i>ex vivo</i> permeation of Iloperidone across goat nasal mucosa was 1270.58 ± 0.023 μg/cm<sup>2</sup> and 1096.13 ± 0.043 μg/cm<sup>2</sup> respectively at the end of 8 h. Studies in RPMI 2650 nasal and Neuro2A brain cell line lines indicated safety of chitosan functionalized transnasal Iloperidone nanoemulsions. Studies in Wistar rats showed increased cataleptic effects, reduced cognitive impairment and anxiety-related behaviour with greater brain accumulation indicating promising potential of this approach in nose to brain drug delivery.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452976","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

Self-Nanoemulsifying/ Self-Assembled Cubic Nanoparticles Lyophilized Tablet: A Novel Biphasic Release Approach to Enhance the Bioavailability of a Lipophilic Drug 自纳米乳化/自组装立方纳米颗粒冻干片剂：提高亲脂性药物生物利用度的新型双相释放方法

IF 3.4 4区医学

AAPS PharmSciTech Pub Date : 2024-10-21 DOI: 10.1208/s12249-024-02952-1

Michael M. Farag, Wessam El-Sebaie, Emad B. Basalious, Omaima N. El-Gazayerly

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