AAPS PharmSciTech最新文献

{"title":"Valsartan Loaded Solid Self-Nanoemulsifying Delivery System to Enhance Oral Absorption and Bioavailability.","authors":"Lusi Chen, Xin Zhang, Jiayu Xie, Tao Xiao, Huiying Zhong, Haibing He, Guoqing Zhang, Hongfei Liu","doi":"10.1208/s12249-024-03032-0","DOIUrl":"https://doi.org/10.1208/s12249-024-03032-0","url":null,"abstract":"<p><p>Valsartan (VST) is an angiotensin II receptor antagonist with low oral bioavailability. The present study developed a solid self-nanoemulsifying drug delivery system (S-SNEDDS) to enhance the oral absorption and bioavailability of VST. VST-loaded liquid SNEDDS (VST@L-SNEDDS) was prepared by investigating the solubility of VST and constructing the pseudo-ternary phase diagrams. The formulation of VST@S-SNEDDS was obtained by adsorbing VST@L-SNEDDS onto a solid carrier. In vitro studies including drug dissolution, stability, cytotoxicity, and Caco-2 uptake of VST@S-SNEDDS were assessed. An in vivo pharmacokinetic study of VST@S-SNEDDS was employed to evaluate the oral bioavailability of VST. VST@L-SNEDDS, with an average particle size of 19.90 nm and zeta potential of -20.57 mV, consisted of 12.37% VST (drug loading), 21.91% ethyl oleate, 45.50% RH 40, and 20.22% Transcutol HP. VST@S-SNEDDS was prepared using Neusilin® UFL2 as a solid adsorbent, which contained VST@L-SNEDDS at 2.28 ± 0.15 g/g. The in vitro release study demonstrated that VST@S-SNEDDS exhibited rapid release characteristic without affecting by the pH of the media, and dissolution rates exceeded 90% within 60 min in different media. The long-term stability of VST@S-SNEDDS was better than that of VST@L-SNEDDS. These two formulations increased the Caco-2 uptake significantly. The area under the drug concentration-time curve (AUC_0-24h) and peak drug concentration in plasma (C_max) of VST@S-SNEDDS increased by 2.28-fold and 4.86-fold compared to raw VST, respectively. The proposed VST@S-SNEDDS represents a novel approach to enhance the oral absorption and bioavailability of VST, providing a promising avenue for hypertension treatment.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 1","pages":"45"},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027668","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}

{"title":"Design and Process Considerations for Preparation of Modified Release Ivermectin and Praziquantel Tablets by Wet Granulation","authors":"R. Gary Hollenbeck,&nbsp;Raafat Fahmy,&nbsp;Marilyn N. Martinez,&nbsp;Ahmed Ibrahim,&nbsp;Stephen W. Hoag","doi":"10.1208/s12249-024-03030-2","DOIUrl":"10.1208/s12249-024-03030-2","url":null,"abstract":"<div><p>Dosage forms containing Ivermectin (IVER) and Praziquantel (PRAZ) are important combination drug products in animal health. Understanding the relationship between products with differing <i>in vitro</i> release characteristics and bioequivalence could facilitate generics. The goal of this study was to create granulations for each active ingredient, with similar release mechanisms, but substantially different <i>in vitro</i> release rates, and then compressing these granulations into tablets with differing release rates. Four granulation formulations were created: fast and modified release for PRAZ and IVER, respectively. The manufacturing process used high shear wet granulation and fluid bed drying, milling and sieving. Solid components, including the granulating agent, were blended in a high shear granulator and then water or a hydroalcoholic solution was added to activate the binder and initiate granule formation. Drying in a fluid bed with inlet air temperature set for 70°C and inlet air volume adjusted as required to maintain fluidization. Milling was performed in a cone mill and classification of final product was done using a vibratory sieve shaker with 18, 20, 40, and 60 mesh sieves. Formulations and processing approaches were successfully developed to produce a collection of PRAZ and IVER granules with differing particle size distributions and <i>in vitro</i> release characteristics. Differences in drug content in the classified granulations were observed and attributed to the low surface energy of PRAZ and the different approaches used to incorporate the active ingredients. The granulations were compressed via compaction simulator and the results show the monolithic tablets had four different release profiles.</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":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995631","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}

{"title":"Human Plasma-Derived Exosomes: A Promising Carrier System for the Delivery of Hydroxyurea to Combat Breast Cancer","authors":"Wajeeha Khalid,&nbsp;Afeefa Aslam,&nbsp;Nadeem Ahmed,&nbsp;Muhammad Sarfraz,&nbsp;Jawad Akbar Khan,&nbsp;Sabeeh Mohsin,&nbsp;Muhammad Shahid Riaz Rajoka,&nbsp;Imran Nazir,&nbsp;Muhammad Imran Amirzada","doi":"10.1208/s12249-024-03028-w","DOIUrl":"10.1208/s12249-024-03028-w","url":null,"abstract":"<div><p>The aim of the present study was to investigate the potential of human plasma derived exosomes for the delivery of hydroxyurea to enhance its therapeutic efficacy in breast cancer. Plasma derived exosomes were isolated using differential centrifugation along with ultrafiltration method. Hydroxyurea was encapsulated in exosomes using a freeze–thaw method. The exosomes and Exo-HU were characterized for their size distribution, drug entrapment efficiency, <i>in-vitro</i> drug release profile, morphological analysis and cytotoxic effects on MCF-7 cell line. The results showed a mean size of 178.8 nm and a zeta potential of -18.3 mV, indicating good stability and 70% encapsulation effectiveness for HU. Exo-HU produced sustained drug release action with a considerable percentage released within 72 h. The morphological analysis indicated that the plasma derived exosomes were spherical, and cup shaped. In cytotoxicity studies on MCF-7 cells, Exo-HU has reduced cell viability compared to HU and blank exosomes. Findings of this study showed that human plasma-derived exosomes have been considered as effective delivery vehicle for hydroxyurea, potentially improving breast cancer treatment outcomes.</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":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995602","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}

{"title":"Development and In-Vitro Tuning of Piperine Containing Solid Lipid Microparticles for the Treatment of Rheumatoid Arthritis","authors":"Muneeba Aziz,&nbsp;Sajid Bashir,&nbsp;Rai Muhammad Sarfraz,&nbsp;Hira Ijaz,&nbsp;Asif Mahmood,&nbsp; Zulcaif,&nbsp;Bilal Haroon,&nbsp;Milad A. Mezher,&nbsp;Mohamed M. Salem,&nbsp;Sami Al Zahrani,&nbsp;Mounir M. Bekhit","doi":"10.1208/s12249-024-03034-y","DOIUrl":"10.1208/s12249-024-03034-y","url":null,"abstract":"<div><p>The current project was designed to develop piperine-loaded solid lipid microparticles (SLMs) to assess the anti-arthritic potential of piperine (PIP). Variable proportions of carnauba wax, beeswax, and tween 80 were employed for preparing SLMs by using the solvent evaporation technique. The developed formulations were subjected to particle size measurements, entrapment efficiency (EE), and zeta potential (ZP) determination. Microparticles were also investigated for piperine-lipid compatibility, thermal analysis, surface morphology, piperine (PIP) release trend, and anti-rheumatic activity in rats. The network's grafting was confirmed by FTIR and XRD results. The thermal stability of the constructed network was confirmed by the DSC and TGA results. SEM findings confirm porous surface morphology. The dissolution experiments on SLMs confirmed the sustained release profile, delivering 87.82% to 94.92% of piperine at 7.4 pH for 24 h. All developed formulations followed a zero-order kinetic model and the Korsmeyer-Peppas model. Furthermore, the anti-rheumatic potentials of piperine from SLMs were also investigated and compared with diclofenac sodium (the standard treatment) in a rat model. The analysis revealed that PIP significantly reduced the severity of arthritis, as confirmed by the findings of multiple arthritic assessment parameters.</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":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995465","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}

{"title":"Transethosomes: A Comprehensive Review of Ultra-Deformable Vesicular Systems for Enhanced Transdermal Drug Delivery","authors":"Raagul Seenivasan,&nbsp;Praveen Halagali,&nbsp;Devika Nayak,&nbsp;Vamshi Krishna Tippavajhala","doi":"10.1208/s12249-024-03035-x","DOIUrl":"10.1208/s12249-024-03035-x","url":null,"abstract":"<div><p>The transdermal route is one of the effective routes for delivering drugs. It also overcomes many limitations associated with oral delivery. One of the limitations of this route is the drug’s poor skin permeability—stratum corneum, the skin’s outermost layer that also acts as a barrier for the drug to penetrate. Traditional liposomal formulation is utilized to overcome these limitations. However, these liposomes also have certain difficulty in delivering drugs across the barriers. Ultra-deformable vesicles are novel vesicular structures that are flexible and stable, they can easily bypass the skin barriers more efficiently and thus enhance bioavailability. These vesicles consist of ethosomes, transethosomes, and transferosomes. Transethosomes are more advanced than other vesicular systems because they contain ethanol, phospholipids, and edge activators, making them more deformable and easier to penetrate deeper skin membranes. These vesicular systems can be prepared by various methods, such as cold, hot, and thin film hydration. Characterization of transethosomes includes vesicular size, zeta potential, polydispersity index and encapsulation efficiency, stability, and drug release studies. These vesicular systems can be utilized to deliver a variety of medications transdermally, including analgesics, antibiotics, and arthritis medications. Despite their promising potential, ethanol-based formulations present several problems requiring additional study. This review aims to describe various vesicular structures that have been used to overcome the barrier for the transdermal delivery of drugs and also describe brief composition, method of preparation, characterization, mechanism of penetration of transethosomes, as well as highlighted various applications of transethosomes in medicine, clinical trials and patents.</p></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-03035-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995234","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}

{"title":"Pharmaceutical Salts: Comprehensive Insights From Fundamental Chemistry to FDA Approvals (2019–2023)","authors":"Mori Dhaval,&nbsp;Kiran Dudhat,&nbsp;Aastha Gadoya,&nbsp;Sunny shah,&nbsp;Trupesh Pethani,&nbsp;Nilesh Jambukiya,&nbsp;Ajay Patel,&nbsp;Chintan Kalsariya,&nbsp;Jainabparvin Ansari,&nbsp;Chetan Borkhataria","doi":"10.1208/s12249-024-03020-4","DOIUrl":"10.1208/s12249-024-03020-4","url":null,"abstract":"<div><p>Pharmaceutical salts are a cornerstone in drug development, offering a robust, economical, and industry-friendly option for improving the crucial physicochemical properties of drugs, particularly solubility and dissolution. This review article explores all critical aspects of salt formation, including its importance, the basic chemistry involved, the principles governing counterion selection, the range of counterions used, and the methods for preparing salts along with their advantages and limitations. Additionally, it explores analytical techniques for confirming salt formation and the different approaches various countries adopt in considering new salts as intellectual property. Furthermore, the review sheds light on US FDA-approved salts from 2019 to 2023, providing a unique perspective by analyzing trends in counterion selection observed in FDA-approved salts during this period. Despite the extensive literature on pharmaceutical salts, a comprehensive review addressing all these critical aspects in a single article with a focus on current trends and particularly on US FDA-approved salts from 2019 to 2023 is lacking. This review bridges this gap by thoroughly exploring all mentioned facets of pharmaceutical salts and providing an up-to-date overview.</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":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994542","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}

{"title":"Dosage Optimization Using Physiologically Based Pharmacokinetic Modeling for Pediatric Patients with Renal Impairment: A Case Study of Meropenem","authors":"Najia Rahim,&nbsp;Muhammad Sarfraz,&nbsp;Abubakar Bello,&nbsp;Syed Baqir Shyum Naqvi","doi":"10.1208/s12249-024-03026-y","DOIUrl":"10.1208/s12249-024-03026-y","url":null,"abstract":"<div><p>The pharmacokinetics of renally eliminated antibiotics can be influenced by changes associated with renal function and development in a growing subject. Little is known about the effects of renal insufficiency on the pharmacokinetics of meropenem in pediatric subjects. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model of meropenem for pediatric patients that can be used to optimize meropenem dosing in pediatric patients with renal impairment (RI). The PBPK model was developed using GastroPlus™ 9.9 based on clinical data obtained from the literature and then scaled to pediatric patients with RI for dose optimization of meropenem. The goodness of fit of the model was assessed by comparing the predicted values of AUC_0-t, AUC_0-α, and C_max with the observed data and the average fold errors (AFE). The AFE values for AUC_0-t, AUC_0-α, and C_max in the pediatric population were measured to be 1.60, 1.08, and 1.48, respectively. In addition, dose optimization was performed in virtual pediatric populations with varying degrees of RI and a dose reduction to 10 mg/kg and 7.5 mg/kg was recommended for moderate and severe RI, respectively. In all virtual pediatric populations with RI, the plasma concentration reached the recommended time above the minimum inhibitory concentration (MIC) at all optimized doses. The developed PBPK model for meropenem provides a quantitative tool to assess the impact of RI on the pharmacokinetics of meropenem in pediatric patients, which may be useful for optimizing the dosing regimen.</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":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994493","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}

{"title":"A New and Safe Delivery of Sildenafil Citrate Co-Evaporate Loaded Emulgels for the Cure of Certain Male Sexual Dysfunctions","authors":"Shaaban K. Osman,&nbsp;Abobakr M. Yassin,&nbsp;Taher M. Yassin,&nbsp;Ahmed M. Mohammed,&nbsp;Ahmed M. Abdelsalam,&nbsp;Wael A. Mahdi,&nbsp;Sultan Alshehri,&nbsp;Mohamed A. El Hamd,&nbsp;Ahmed A. H. Abdellatif,&nbsp;Mohammed A. Amin,&nbsp;Emad A. Taha","doi":"10.1208/s12249-024-03027-x","DOIUrl":"10.1208/s12249-024-03027-x","url":null,"abstract":"<div><p>The present work focuses on the production of sildenafil co-evaporates loaded emulgels as topical dosage forms for the treatment of premature ejaculation and erectile dysfunction. Topical administration of sildenafil citrate (SILD) co-evaporates is expected to improve the bioavailability profile of the drug and to avoid the severe side effects accompanying the traditional SILD dosage forms, especially for prohibited cardiovascular cases. Firstly, the solubility of SILD was improved via solid dispersion via co-evaporation technique using PEG-5KDa and PVP-K90 as hydrophilic carriers. The modified co-evaporates were characterized by DSC, XRD, and solubility studies. Different emulgels, loaded with SILD co-evaporates, were formulated and characterized by different analyses including the viscosity, stability, spreadability, and <i>in vitro</i> release studies. Finally, the clinical activity of the chosen formula was accomplished via the application of the emulgels on volunteers suffering from erectile dysfunction. The results showed that the prepared SILD/PVP K90 of 1:2 w/w ratio exhibited the highest solubility and dissolution rate. All formulated emulgels exhibited good physicochemical properties. Especially, the emulgel formula composed of 2%w/v HPMC, loaded with SILD /PVP- K90, revealed the highest release rate. The release mechanism of SILD from emulgels fits with the Korsmeyer Peppas mechanism. The results of <i>in vivo</i> studies indicated a significant improvement of both IVLT and IIEF-5 parameters in mild to moderate ED, accompanied by PE. The modified SILD emulgel is an alternative promising and safe transdermal drug delivery system for the management and treatment of mild to moderate ED with PE.</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":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994492","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}

{"title":"A Novel Facile and Efficient Prophylaxis Avenue of Chitosan Oligosaccharide/PLGA Based Polydatin Loaded Nanoparticles Against Bleomycin-Induced Lung Inflammation in Experimental Rat Model","authors":"Ahmed Nashaat Alnagar,&nbsp;Amira Motawea,&nbsp;Randa A. Zaghloul,&nbsp;Mamdouh Eldesoqui,&nbsp;Irhan Ibrahim Abu Hashim","doi":"10.1208/s12249-024-03022-2","DOIUrl":"10.1208/s12249-024-03022-2","url":null,"abstract":"<div><p>Lung inflammation is a hallmark of several respiratory diseases. Despite the great effectiveness of the synthetic antiinflammatory agents, they cause potential side effects. Polydatin (PD), a natural phytomedicine, has antioxidant and antiinflammatory effects. Its clinical applications are hindered due to poor aqueous solubility, low bioavailability, and rapid metabolism by first-pass effect. Herein, we report the development of a novel chitosan oligosaccharide-coated PD-loaded Poly dl-lactide-co-glycolide nanoparticles (COS-coated PD/PLGA NPs) against a bleomycin-induced pulmonary inflammation in a rat model. The NPs exhibited a small particle size of 188.57 ± 5.68 nm and a high zeta potential of + 18.13 ± 2.75 mV with spherical architecture and sustained release pattern of PD. <i>In vivo</i> studies in bleomycin-induced lung inflammation in a rat model revealed the superior prophylactic activity of COS-coated PD/PLGA NPs over the free drug (PD) as demonstrated by histopathological and immunohistochemical analyses, alongside biochemical assays evaluating oxidative stress biomarkers and inflammatory cytokine levels. Overall, the optimized COS-coated PD/PLGA NPs formulation offers a promising prophylactic platform against many respiratory 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":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-024-03022-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994428","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}

{"title":"Pediatric Formulation Optimization Using a Rational Design: Exploring Amorphous Solid Dispersion Technology with Terbinafine Hydrochloride as a Case Study","authors":"Izabelle Amorim Ferreira Boza,&nbsp;Stéfani Laise da Silva,&nbsp;Nicolly Bittencourt Guedes,&nbsp;Giovana Carolina Bazzo,&nbsp;Hellen Karine Stulzer","doi":"10.1208/s12249-024-03012-4","DOIUrl":"10.1208/s12249-024-03012-4","url":null,"abstract":"<div><p>Developing orally administered pediatric formulations presents significant challenges due to the unique characteristics of pediatric patients. Terbinafine hydrochloride (TER), a powerful antifungal agent, is effective against various fungal infections, including <i>Tinea capitis</i>, which is common in children. However, its low aqueous solubility necessitates innovative pharmaceutical strategies to enhance its effectiveness. This study describes a rational approach to selecting suitable carriers, approved for use in children, to increase the apparent solubility of TER and to guide the development of amorphous solid dispersions containing this drug. Assessments of solubility parameters, equilibrium solubility measurements, and calculations of pediatric dose numbers guided formulation development using theoretical and experimental methodologies. Carriers like Plasdone S-360 ULTRA®, HPMCAS L, and Soluplus® demonstrated favorable solubility parameter values with TER, indicating potential for drug solubilization. The solubility of TER was strongly dependent on pH. In buffer pH 6.5 containing 10% (w/v) of Soluplus®, TER presented the highest solubility value. The solid-state characterization techniques employed to assess the precipitate formed after equilibrium solubility studies during preformulation demonstrated that there were no phase transitions and no significant interactions between the drug and the evaluated carriers. Furthermore, the results demonstrate that Soluplus® achieved the lowest dose number (0.23) for pediatric patients over 6 years old. So, it was selected for preparing the amorphous solid dispersion via spray drying, which significantly enhanced the apparent solubility of TER while maintaining prolonged supersaturation, offering a promising alternative for developing solid formulations of this drug, particularly for pediatric patients, as it aims to improve oral bioavailability.</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":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994426","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}