Journal of pharmaceutical sciences最新文献

{"title":"Development of polylactic acid microneedles for enhanced transdermal delivery of desmopressin peptides: A computational study","authors":"Amirhossein Dashti ,&nbsp;Milad Salimibani ,&nbsp;Yegane Fanaei","doi":"10.1016/j.xphs.2025.103777","DOIUrl":"10.1016/j.xphs.2025.103777","url":null,"abstract":"<div><div>Addressing the challenges associated with traditional injection therapies, this research marks a significant advancement in personalized and targeted therapeutic interventions, offering improved efficacy, convenience, and safety for patients undergoing peptide-based treatments. This article presents a research study on the development and assessment of polylactic acid (PLA) microneedles for enhancing the delivery of proteins and peptides, mainly focusing on the transdermal administration of desmopressin. Using simulations with COMSOL multiphysics software, it has been shown that PLA microneedles have excellent durability and controlled drug delivery capabilities, which promise efficient and patient-friendly transdermal drug delivery applications. Computational modeling results highlighted the dynamic behavior of desmopressin flow within the microneedle system, emphasizing accelerated drug transport capabilities. The utilization of dissolving microneedles in this study underscores the potential of microneedle technology as a promising solution for enhancing transdermal drug permeation, particularly for hydrophilic and macromolecular substances like proteins and peptides, thus opening new avenues for effective drug delivery systems.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103777"},"PeriodicalIF":3.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight on a novel drug-drug salt levofloxacin-flufenamate crystal structures, physicochemical properties, potency, and antiinflammation improvement","authors":"Ilma Nugrahani ,&nbsp;Hidehiro Uekusa ,&nbsp;Yutong Wu ,&nbsp;Takaaki Hori ,&nbsp;Hanna Auliaurridho ,&nbsp;Diar Herawati ,&nbsp;Febrina Ester Panjaitan ,&nbsp;Afrilia Garmana ,&nbsp;Marlia Singgih Wibowo","doi":"10.1016/j.xphs.2025.103779","DOIUrl":"10.1016/j.xphs.2025.103779","url":null,"abstract":"<div><div>This study aimed to determine the three-dimensional structure, scale-up process, and investigate the stability, potency, and anti-inflammatory profile of a new multicomponent salt, levofloxacin–flufenamate, abbreviated as LFN-FA. Initially, the molar ratio stoichiometry was screened, and the single crystal was prepared by slow evaporation. Single-crystal X-ray diffractometry (SCXRD) was used to determine the three-dimensional structure. Subsequently, the scale-up process was conducted using wet-grinding and hot-melting techniques to produce samples for stability, solubility, potency, and anti-inflammatory tests. SCXRD data proved that the multi-component structure of LFN-FA was a hydrated salt, consisting of the ionized carboxyl group of flufenamic acid and the amine group of levofloxacin, with a water molecule in a (1:1:1) molar proportion. Furthermore, scale-up by wet grinding successfully produced the anhydrous salt beside the LFN-FA hydrate, which both were physically stable under the open container conditions at room temperature (25–30 °C/ 75–85 %RH) for 4 weeks. They increased the solubility of flufenamic acid, with the anhydrous form demonstrating twice the solubility of the hydrate form. Hence, anhydrous LFN-FA was selected for evaluation of its chemical stability, in-vitro antimicrobial potency, and anti-inflammatory effect, all of which met the expected improvements. These experiments showed that this unique antibiotic-anti-inflammatory combination, LFN-FA, in a multi-component salt structure, could be developed further in the dosage form formulation.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103779"},"PeriodicalIF":3.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal delivery of kaempferol via magnesomes for brain seizure treatment: Design, characterization, and biodistribution studies","authors":"Shymaa Hatem ,&nbsp;Marwa Eid Sayyed ,&nbsp;Maha El-Kayal","doi":"10.1016/j.xphs.2025.103780","DOIUrl":"10.1016/j.xphs.2025.103780","url":null,"abstract":"<div><div>The current study aims to develop phospholipid magnesomes retaining the inherent neuroprotective activities of kaempferol as a proposed treatment approach for epilepsy. Magnesomes were prepared using varied amounts of phospholipid, magnesium sulfate and poloxamer 188, and evaluated on <em>in-vitro</em> and <em>in-vivo</em> levels. The prepared vesicles possessed nanosizes (112-625 nm), negative charges (-16 to -20 mV), and entrapment efficiency (80–96 %) with negligible changes in their colloidal properties after 3 months’ storage. Magnesomes showed sustained release of kaempferol as well as superior permeability relative to drug solution. Radiolabeling of kaempferol with iodine-131 was successfully performed using electrophilic substitution. The superior brain uptake of intranasally delivered ¹³¹I-kaempferol-magnesomes containing 3.13 µg/20µl of kaempferol compared to intravenous and intranasal solutions was demonstrated employing biodistribution and pharmacokinetic tests conducted using Swiss Albino male mice. Brain to blood ratio of the intranasally administered kaempferol was significantly higher compared to intravenous injection showing uptake of 9.9 ± 0.3 % injected dose per gram organ at the first 5 min ensuring a rapid onset of action. The drug targeting efficiency and nose to brain direct transport percentages of ¹³¹I- kaempferol-magnesomes were 215.0 and 87.0 %, respectively with relative bioavailability of 810.24 ± 119.1 %. Accordingly, intranasal kaempferol-magnesomes showed effectiveness in brain targeting and could be beneficial for managing epileptic seizures.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103780"},"PeriodicalIF":3.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly increasing solubility of clofazimine, an extremely water-insoluble basic drug, in lipid-based SEDDS using digestion products of long-chain lipids","authors":"Hari P. Kandagatla ,&nbsp;Mufaddal H. Kathawala ,&nbsp;Amber Syed ,&nbsp;Tatjana Ž. Verbić ,&nbsp;Alex Avdeef ,&nbsp;Martin Kuentz ,&nbsp;Abu T.M. Serajuddin","doi":"10.1016/j.xphs.2025.103782","DOIUrl":"10.1016/j.xphs.2025.103782","url":null,"abstract":"<div><div>Clofazimine (CFZ) is a highly effective antibiotic against leprosy and drug-resistant tuberculosis and is on the WHO List of Essential Drugs. However, no CFZ product with optimal bioavailability is available worldwide. The manufacturer withdrew its only marketed product, presumably due to poor and erratic bioavailability because of extremely low aqueous solubility in the gastrointestinal pH range. We developed a self-emulsifying drug delivery system (SEDDS) using a lipid digestion product (LDP) containing glyceryl monooleate and oleic acid at ∼1:2 molar ratio to increase drug solubility and ensure rapid dispersion into microemulsion. While solubilities of CFZ in glyceryl monooleate, glyceryl trioleate, and two common surfactants (Tween 80 and Kolliphor EL) were comparatively low (&lt;15 mg/g), oleic acid provided a very high solubility of ∼500 mg/g. Because of the presence of oleic acid, the clofazimine solubility in SEDDS containing a 50:50 w/w mixture of LDP and surfactants increased to 130 mg/g. Two formulations having 50 or 100 mg CFZ in one gram of SEDDS were developed. They dispersed rapidly and almost completely in simulated intestinal fluid and in the USP pH 6.8 phosphate buffer containing 3 mM sodium taurocholate. There was some precipitation of CFZ as the HCl salt at low gastric pH during dispersion testing, but the effect could be avoided using enteric-coated capsules. Thus, an enteric-coated lipid-based formulation for CFZ with as high as 100 mg/g drug loading was developed, providing complete drug release and producing microemulsions under intestinal pH conditions.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103782"},"PeriodicalIF":3.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using response surface methodology to quantify iron oxide levels needed to protect photolabile active pharmaceutical ingredients in oral solid dosage forms","authors":"Ryan Kawakita ,&nbsp;Diana Sperger ,&nbsp;Ben Chal ,&nbsp;Julie Fogarty ,&nbsp;Michael McCormick ,&nbsp;Daniel To ,&nbsp;David Ferrizzi ,&nbsp;Ali Rajabi-Siahboomi","doi":"10.1016/j.xphs.2025.103778","DOIUrl":"10.1016/j.xphs.2025.103778","url":null,"abstract":"<div><div>Titanium dioxide (TiO₂) is a commonly used excipient in pharmaceutical products. It functions as a pigment and opacifier in film coatings, providing photoprotection and enabling consistent product appearance for oral solid dosage forms. TiO₂ was banned in foods by the European Commission in 2022 and the decision on a ban in medicines will be revisited in early 2025. There is an urgent need to identify TiO₂ alternatives. Currently, no single excipient has been found to directly replace TiO₂ in existing film-coating systems. Iron oxide pigmentation offers a potential solution for addressing the role TiO₂ plays in photoprotection. Using a mixture model design of experiments (DOE), three iron oxides – red, yellow, and black – were assessed on their efficacy in photoprotection. A model photolabile active pharmaceutical ingredient (API) was prepared into tablets and coated with varied iron oxide concentrations in a PVA-based titanium dioxide-free (TF) film-coating. Red and yellow iron oxide were found to significantly reduce total photodegradation products. By including 1–1.5 % red or yellow iron oxide in this TF film-coating, 75–85 % photoprotection was achieved, while 2 % or greater red iron oxide had nearly complete photoprotection. A second photolabile API was tested to confirm the results of the DOE.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103778"},"PeriodicalIF":3.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the pore structure variance of lyophilized cakes from microcollapse, controlled ice nucleation, and protein concentration changes","authors":"Lisa Ma ,&nbsp;Lokesh Kumar ,&nbsp;Fredric Lim ,&nbsp;Shawn Zhang ,&nbsp;Jeffrey Wong ,&nbsp;Phillip D. Yawman ,&nbsp;Debby Chang","doi":"10.1016/j.xphs.2025.103775","DOIUrl":"10.1016/j.xphs.2025.103775","url":null,"abstract":"<div><div>This study investigates the application of X-ray microscopy (XRM) as an advanced characterization tool for optimizing lyophilization cycles in pharmaceutical formulations. Utilizing non-invasive, high-resolution imaging, XRM provided comprehensive insights into the macro- and microstructural features of lyophilized cakes, revealing distinct differences attributable to lyophilization processing. High primary drying temperatures and aggressive conditions led to microstructural alterations, including fractures and microcollapse, while conservative drying methods resulted in more uniform and homogeneous structure. The controlled ice nucleation (CIN) process notably enhanced sublimation rates by forming extensive macroporous zones. Calibrated intensity analysis via XRM detected variations in solid content, and high-resolution imaging highlighted subtle microstructural differences among samples, contributing to a deeper understanding of cake properties. Surface area measurements obtained from XRM showed a strong correlation with conventional BET analysis, validating its quantitative accuracy. Additionally, simulated diffusivity derived from XRM data correlated well with dry layer resistance values from thermocouple measurements, underscoring its utility in evaluating mass transport behaviors. XRM's non-destructive nature and detailed imaging capabilities make it a valuable complementary tool to existing characterization techniques, enabling more efficient cycle development and optimization.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103775"},"PeriodicalIF":3.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioorthogonal catalytic microvesicle-mediated prodrug activation against liver cancer","authors":"Xiaotian Wan ,&nbsp;Xiyu Liu ,&nbsp;Pan Wu ,&nbsp;Yongmei Li,&nbsp;Yuanyuan Shi,&nbsp;Yueli Nie,&nbsp;Keyong Zhang,&nbsp;Ze Jin,&nbsp;Ruiyun Song,&nbsp;Zhikun Zhang,&nbsp;Lu Gan,&nbsp;Jian He","doi":"10.1016/j.xphs.2025.103774","DOIUrl":"10.1016/j.xphs.2025.103774","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Exploring the role and mechanism of a novel bioorthogonal system using transition metals as catalysts in the treatment of hepatocellular carcinoma (HCC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Initially, a catalytic ruthenium (Ru) complex and the substrate alloc-RH 110 were synthesized, followed by the identification of their structures utilizing mass spectrometry and nuclear magnetic resonance (NMR) techniques. The catalytic efficacy of the Ru complex was then assessed using a fluorescence spectrophotometer. Subsequently, employing HepG2 cells as the cellular source, cell-derived vesicles encapsulating the Ru complexes, designated as EVs@Ru, were prepared. The EVs@Ru were characterized by measuring their particle size and Zeta potential, observing morphological features under transmission electron microscopy (TEM), and detecting specific protein expressions via Western blot analysis. Drug loading within the EVs@Ru was quantified using inductively coupled plasma mass spectrometry (ICP-MS), and their catalytic efficiency was evaluated. In vitro, the low-activity prodrug alloc-DOX was synthesized and its toxicity, along with the drug concentration in EVs@Ru, was determined. Further, the catalytic cytotoxicity of alloc-DOX against HepG2 cells encapsulated in EVs@Ru was analyzed through microscopic observation, CCK-8 assays, and apoptosis experiments. For in vivo studies, a tumor-bearing mouse model was established using human liver cancer HepG2 cells to observe the antitumor effects. Finally, the primary organs of each group of tumor-bearing mice were assessed for in vivo safety.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;ESI-MS and 1H NMR confirmed the accurate structure of Ru complexes and alloc-RH 110. The Ru complexes achieved full catalytic conversion of alloc-RH 110 within 24 hours. EVs and EVs@Ru exhibited particle sizes of ∼116.85 nm and ∼281.88 nm, respectively, with Zeta potentials of ∼-20.86 mV and ∼-25.89 mV, both appearing quasi-circular under TEM. WB analysis verified the presence of vesicle-specific marker proteins in both, confirming their cell-derived nature. ICP-MS determined a drug loading of 21.90 μg/mL for EVs@Ru, with an encapsulation efficiency of ∼24.86%. Fluorescence spectrophotometry demonstrated 100% catalytic efficiency for EVs@Ru. Synthetic alloc-DOX validated by 1H NMR and ESI-MS matched literature data. MTT and CCK-8 assays confirmed low toxicity for alloc-DOX and Ru complexes, setting the experimental drug concentration at 4μM. In vitro, the EVs@Ru+alloc-DOX group exhibited potent HepG2 cell killing and apoptosis. In vivo, this group significantly inhibited tumor growth in tumor-bearing mice, with no observed toxicity to vital organs, indicating good biosafety.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The integration of bio-derived microvesicles (MVs) with transition metal catalysts has resulted in a biologically orthogonal system for efficient Ru complex delivery to tumor sites. This system facilit","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103774"},"PeriodicalIF":3.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating ICH Q2(R2) compliance in analytical method validation: A gap analysis toolkit to streamline risk assessment and change management","authors":"Brianna Cassidy ,&nbsp;Timothy Bloomingdale ,&nbsp;Judy Carmody","doi":"10.1016/j.xphs.2025.103749","DOIUrl":"10.1016/j.xphs.2025.103749","url":null,"abstract":"<div><div>The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) officially adopted Q2(R2) and Q14 as harmonized guidelines on November 1, 2023. Updated guidance for validating analytical methods is provided in Q2(R2), while Q14 introduces, for the first time, comprehensive guidance on the development of analytical methods. Multiple regulatory authorities have officially incorporated Q2(R2) and Q14, and many others are in the process. However, a detailed list of differences between Q2(R1) and Q2(R2) has yet to be made available. The toolkit presented here is designed to streamline risk assessment and change management efforts for updating systems based on long-established Q2(R1) guidance; 56 specific omissions, expansions, and additions are identified, and a process for navigating these changes is proposed. Suggestions for improving Q2(R2) and related chapters (including Q7, <em>Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients Guidance for Industry</em>) are also discussed. Given the close relationship between analytical method development and validation, many aspects of Q14 are included in Q2(R2) and are therefore described here.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103749"},"PeriodicalIF":3.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro characterization of SLCO2B1 genetic variants","authors":"Alli Sinokki ,&nbsp;Annika Miinalainen ,&nbsp;Saara Kivioja ,&nbsp;Wilma Kiander ,&nbsp;Kati-Sisko Vellonen ,&nbsp;Madhushree Bhattacharya ,&nbsp;Mikko Gynther ,&nbsp;Kristiina M. Huttunen ,&nbsp;Seppo Auriola ,&nbsp;Mikko Niemi ,&nbsp;Heidi Kidron","doi":"10.1016/j.xphs.2025.103772","DOIUrl":"10.1016/j.xphs.2025.103772","url":null,"abstract":"<div><div>OATP2B1, encoded by <em>SLCO2B1</em>, is a drug transporter expressed widely throughout the body in tissues such as the intestine and liver. Genetic variation of this transporter may lead to altered disposition of OATP2B1 substrate drugs, but especially the effects of rare variants are poorly understood. The aim of this study was to characterize the effects of naturally occurring missense single nucleotide variants of <em>SLCO2B1</em> (c.601G&gt;A, c.935G&gt;A, c.953C&gt;T, c.1175C&gt;, c.1457C&gt;T, c.1559G&gt;C, c.1596C&gt;A, and the c.601G&gt;A + c.935G&gt;A haplotype) on the <em>in vitro</em> functionality of OATP2B1. To characterize transport activity, cellular uptake of dibromofluorescein, 5-carboxyfluorescein, estrone sulfate, and rosuvastatin was compared in OATP2B1 reference- and variant-expressing HEK293 cells. The abundance of OATP2B1 variants in HEK293 crude membrane preparations was quantified with LC-MS/MS-based quantitative targeted absolute proteomics analysis. Variant c.1559G&gt;C impaired OATP2B1-mediated uptake of all tested substrates almost completely, but protein abundance was not reduced to the same extent. Other studied variants had comparable or only modestly reduced protein abundance and transport function compared to reference OATP2B1. These results can be utilized to understand findings from clinical pharmacogenetic studies. More importantly, the results can aid in predicting the consequences of rare variants, such as the loss-of-function variant c.1559G&gt;C, which can be difficult to detect in clinical studies.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103772"},"PeriodicalIF":3.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the solubility and bioavailability of itraconazole through pharmaceutical cocrystallization: A promising strategy for drug formulation","authors":"Meet Chhatbar ,&nbsp;Chetan Borkhataria ,&nbsp;Om Patel ,&nbsp;Komal Raichura ,&nbsp;Trupesh Pethani ,&nbsp;Ghanshyam Parmar ,&nbsp;Dhaval Mori ,&nbsp;Ravi Manek","doi":"10.1016/j.xphs.2025.103770","DOIUrl":"10.1016/j.xphs.2025.103770","url":null,"abstract":"<div><div>Itraconazole, a potent antifungal agent, is classified as a Biopharmaceutics Classification System (BCS) Class II drug, exhibiting high permeability but poor aqueous solubility, which significantly limits its bioavailability and therapeutic efficacy. Conventional solubility enhancement techniques such as salt formation, particle size reduction, and encapsulation have shown limited success due to the drug's non-ionizable nature and pH-dependent solubility. Cocrystallization has emerged as a promising pharmaceutical strategy to address these limitations by modifying the crystal lattice structure through non-covalent interactions with pharmaceutically acceptable co-formers. This study explores the formulation of Itraconazole cocrystals with various co-formers to enhance its solubility, dissolution rate, and micromeritic properties, thereby improving its processability in solid dosage forms. The optimized cocrystal formulation (B16) demonstrated a 2.4-fold increase in solubility in 0.1 N HCl (60.47 ± 2.7 µg/mL) and a 25.77-fold increase in phosphate buffer (pH 6.8, 60.57 ± 5.64 µg/mL) compared to pure Itraconazole. The dissolution rate was also significantly improved, with 40.12% drug release in 120 minutes in acidic medium, compared to 32.65% for pure Itraconazole. Furthermore, pharmacokinetic studies in rats revealed a 2.8-fold increase in AUC (3717.58 ng·h/mL) and a C_max of 206.86 ng/mL, compared to 88.06 ng/mL for the pure drug. The study further examines the industrial feasibility of cocrystallization as an innovative approach for optimizing poorly soluble drugs in commercial formulations. The results highlight the potential of cocrystal technology in overcoming formulation challenges and advancing the development of more effective and patient-friendly antifungal therapies.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 6","pages":"Article 103770"},"PeriodicalIF":3.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}