Pub Date : 2026-01-08DOI: 10.1208/s12249-025-03289-z
Tahir Khuroo, Linh H. Maracchini, Ziyaur Rahman, Mansoor A. Khan
This study investigated effect of formulation and process variables on the quality attributes of lamivudine printlets manufactured by binder jetting 3D printing method. The variables studied through fractional design of experiment were number of solvent sprays, delay time, powder layer thickness, drying temperature and hydroxypropyl methyl percentage. The printlets were assessed for hardness, disintegration time (DT), and dissolution and chemical information by X-ray powder diffraction (XRPD) and Fourier transformed spectroscopy, near infrared hyperspectroscopy, and taste evaluation by electronic tongue. The printlet hardness and DT ranged from 2.5 to 21.1 N, and 2.3 to 317 s, respectively. The dissolution profile met USP specifications of > 85% drug dissolved in 30 min. XRPD indicated partial amorphization of the drug in the printlets and hyperspectroscopy indicated uniform distribution of the components in the formulation. Stability data indicated no significant change in quality of the printlets in terms of dissolution and assay. Excipients used in the formulation reduced the bitterness of the drug to some degree. In summary, binder jetting can be used to print personalized medication with quality control characteristics.
{"title":"Effect of Process and Formulation Variables on Quality, Stability, and Taste of Lamivudine Printlets Manufactured by Binder Jetting 3D Printing Method","authors":"Tahir Khuroo, Linh H. Maracchini, Ziyaur Rahman, Mansoor A. Khan","doi":"10.1208/s12249-025-03289-z","DOIUrl":"10.1208/s12249-025-03289-z","url":null,"abstract":"<div><p>This study investigated effect of formulation and process variables on the quality attributes of lamivudine printlets manufactured by binder jetting 3D printing method. The variables studied through fractional design of experiment were number of solvent sprays, delay time, powder layer thickness, drying temperature and hydroxypropyl methyl percentage. The printlets were assessed for hardness, disintegration time (DT), and dissolution and chemical information by X-ray powder diffraction (XRPD) and Fourier transformed spectroscopy, near infrared hyperspectroscopy, and taste evaluation by electronic tongue. The printlet hardness and DT ranged from 2.5 to 21.1 N, and 2.3 to 317 s, respectively. The dissolution profile met USP specifications of > 85% drug dissolved in 30 min. XRPD indicated partial amorphization of the drug in the printlets and hyperspectroscopy indicated uniform distribution of the components in the formulation. Stability data indicated no significant change in quality of the printlets in terms of dissolution and assay. Excipients used in the formulation reduced the bitterness of the drug to some degree. In summary, binder jetting can be used to print personalized medication with quality control characteristics.</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":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930540","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}
Pub Date : 2026-01-08DOI: 10.1208/s12249-025-03276-4
Subhrasima Nayak, Arka Karmakar, Sampada Shinde, Lalit Kumar
Myopathies, joint impairment, muscle spasm, and torn muscles cause an excessive amount of musculoskeletal inflammation, which ultimately causes muscular soreness and stiffness, leading to difficulty in mobility. NSAIDs can suppress the COX enzyme, crucial for converting arachidonic acid into prostaglandin-E2. Oxidative burden increases during impaired health conditions, alleviating and prolonging the inflammatory phase and pain sensation. DA is a widely accepted NSAID that functions as a non-specific inhibitor of COX and is reported to have antioxidant properties. However, it has low solubility and severe adverse effects when used at high doses over a long-term therapy. Thus, the objective of this study is to develop a DA-loaded transferosomal gel with promising anti-inflammatory and antioxidant activity that resembles the commercially available gel, with improved solubility, decreasing the higher dose regimen, minimize potential side effects, and facilitating muscular pain relief over a long period of time. Transferosomes were prepared with a modified thin film hydration technique. The optimized formulation attained the desired particle size, PDI, and zeta potential with high entrapment. The transferosomal gel was investigated for physical characterization, in vitro diffusion, ex vivo permeation, and cellular studies. A cumulative drug release of 92.89 ± 4.21% was achieved after 10 h. The transferosomal gel demonstrated exceptional regulated drug diffusion of 90.68 ± 1.42% over 24 h and permeation of 99.57 ± 6.41% over 48 h. This formulation also exhibited better antioxidant and anti-inflammatory activities than the marketed gel after investigation of in vitro cellular studies. Based on acquired results, it is concluded that DA-loaded transferosomal gel may be potentially effective for reducing musculoskeletal inflammation and providing pain relief.
{"title":"Development of Diclofenac Acid Encapsulated Transferosomal gel with Enhanced Antioxidant and Anti-Inflammatory Activities for the Management of Musculoskeletal Pain","authors":"Subhrasima Nayak, Arka Karmakar, Sampada Shinde, Lalit Kumar","doi":"10.1208/s12249-025-03276-4","DOIUrl":"10.1208/s12249-025-03276-4","url":null,"abstract":"<div><p>Myopathies, joint impairment, muscle spasm, and torn muscles cause an excessive amount of musculoskeletal inflammation, which ultimately causes muscular soreness and stiffness, leading to difficulty in mobility. NSAIDs can suppress the COX enzyme, crucial for converting arachidonic acid into prostaglandin-E<sub>2</sub>. Oxidative burden increases during impaired health conditions, alleviating and prolonging the inflammatory phase and pain sensation. DA is a widely accepted NSAID that functions as a non-specific inhibitor of COX and is reported to have antioxidant properties. However, it has low solubility and severe adverse effects when used at high doses over a long-term therapy. Thus, the objective of this study is to develop a DA-loaded transferosomal gel with promising anti-inflammatory and antioxidant activity that resembles the commercially available gel, with improved solubility, decreasing the higher dose regimen, minimize potential side effects, and facilitating muscular pain relief over a long period of time. Transferosomes were prepared with a modified thin film hydration technique. The optimized formulation attained the desired particle size, PDI, and zeta potential with high entrapment. The transferosomal gel was investigated for physical characterization, <i>in vitro</i> diffusion, <i>ex vivo</i> permeation, and cellular studies. A cumulative drug release of 92.89 ± 4.21% was achieved after 10 h. The transferosomal gel demonstrated exceptional regulated drug diffusion of 90.68 ± 1.42% over 24 h and permeation of 99.57 ± 6.41% over 48 h. This formulation also exhibited better antioxidant and anti-inflammatory activities than the marketed gel after investigation of <i>in vitro</i> cellular studies. Based on acquired results, it is concluded that DA-loaded transferosomal gel may be potentially effective for reducing musculoskeletal inflammation and providing pain relief.</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":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930525","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}
Microneedle-mediated transdermal delivery of phytoconstituents represents a sophisticated and emerging paradigm in dermatological therapeutics, bridging the pharmacological efficacy of plant-derived bioactive with the precision of advanced biomedical engineering. Conventional topical dosage forms are often constrained by the formidable barrier function of the stratum corneum, instability of phytochemicals, and suboptimal patient adherence. Microneedle arrays circumvent these limitations by creating transient microchannels that enable minimally invasive, painless, and controlled delivery of therapeutics into the viable epidermal and dermal layers. The bioactive compounds such as curcumin, resveratrol, asiaticoside, and glycyrrhizin exhibit multifaceted pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and pro-regenerative effects, which are beneficial for the management of cutaneous pathologies such as psoriasis, eczema, acne vulgaris, and chronic ulcerations. The incorporation of these phytoconstituents into dissolving or hydrogel-forming microneedles enhances their physicochemical stability, facilitates sustained and localized drug release, and minimizes systemic exposure, thereby improving therapeutic efficacy and safety. The utilization of natural, biodegradable, and biocompatible polymers such as chitosan, hyaluronic acid, silk fibroin, and alginate, further augments the structural integrity and bioperformance of microneedle systems while aligning with eco-sustainable pharmaceutical design principles. This integrative strategy signifies a pivotal advancement toward personalized dermatological interventions, enabling precise dosing and targeted pharmacokinetics. The future research should emphasize material innovation, in vivo pharmacodynamic assessment, and large-scale translational studies to validate the clinical potential of phytoconstituent-loaded microneedles as next-generation bioresponsive platforms for skin therapeutics.
{"title":"Smart Stings of Nature: Harnessing Microneedles Assisted Targeted Phytoconstituent Delivery for Dermatological Disorders","authors":"Akshay Kumar, Suresh Babu Kondaveeti, Arpan Kumar Tripathi, Mohit Agrawal, Thakur Gurjeet Singh, Devesh Kumar, Mohit Kumar","doi":"10.1208/s12249-025-03311-4","DOIUrl":"10.1208/s12249-025-03311-4","url":null,"abstract":"<div><p>Microneedle-mediated transdermal delivery of phytoconstituents represents a sophisticated and emerging paradigm in dermatological therapeutics, bridging the pharmacological efficacy of plant-derived bioactive with the precision of advanced biomedical engineering. Conventional topical dosage forms are often constrained by the formidable barrier function of the <i>stratum corneum</i>, instability of phytochemicals, and suboptimal patient adherence. Microneedle arrays circumvent these limitations by creating transient microchannels that enable minimally invasive, painless, and controlled delivery of therapeutics into the viable epidermal and dermal layers. The bioactive compounds such as curcumin, resveratrol, asiaticoside, and glycyrrhizin exhibit multifaceted pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and pro-regenerative effects, which are beneficial for the management of cutaneous pathologies such as psoriasis, eczema, acne vulgaris, and chronic ulcerations. The incorporation of these phytoconstituents into dissolving or hydrogel-forming microneedles enhances their physicochemical stability, facilitates sustained and localized drug release, and minimizes systemic exposure, thereby improving therapeutic efficacy and safety. The utilization of natural, biodegradable, and biocompatible polymers such as chitosan, hyaluronic acid, silk fibroin, and alginate, further augments the structural integrity and bioperformance of microneedle systems while aligning with eco-sustainable pharmaceutical design principles. This integrative strategy signifies a pivotal advancement toward personalized dermatological interventions, enabling precise dosing and targeted pharmacokinetics. The future research should emphasize material innovation, <i>in vivo</i> pharmacodynamic assessment, and large-scale translational studies to validate the clinical potential of phytoconstituent-loaded microneedles as next-generation bioresponsive platforms for skin therapeutics.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929894","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}
Pub Date : 2026-01-08DOI: 10.1208/s12249-025-03303-4
Rosilene Ribeiro de Sousa, Matheus Oliveira do Nascimento, Leandro Josuel da Costa Santos, Francisco Gesley de Sousa Abreu, André Luiz Pinheiro de Moura, Daniele Costa Lopes, Karla Germana dos Reis Bacelar, Rita de Cássia Vianna de Carvalho, Paulline Paiva Mendes de Souza Leal, Charllyton Luis Sena da Costa, Vitória de Cássia Coelho Rodrigues, Fernando Aécio de Amorim Carvalho, Michel Muálem de Moraes Alves, André Luis Menezes Carvalho
American Tegumentary Leishmaniasis (ATL) is a zoonotic disease characterized by polymorphic cutaneous and mucosal manifestations, caused by protozoa of the genus Leishmania and transmitted through the bite of sandflies. Current treatment relies on pharmacotherapy with drugs such as amphotericin B (AmB), which is limited by adverse effects. Novel topical formulations of AmB, including bigels, have been investigated as alternatives for ATL therapy, aiming to achieve local efficacy with reduced toxicity and lower cost. This study sought to develop and characterize an AmB loaded-bigel for topical application and to evaluate its in vivo antileishmanial activity. The formulations were characterized by organoleptic analysis, pH, stability, oil retention capacity, swelling, spreadability, and texture profile. In vitro drug release and skin permeation were assessed using Franz diffusion cells and murine skin, while the ocular irritation potential was evaluated through the HET-CAM assay. In vivo efficacy was tested in BALB/c mice infected with Leishmania amazonensis, monitoring lesion progression and parasite burden. Treatment with the AmB loaded-bigel resulted in a 74.1% reduction in parasite load. Overall, the bigel demonstrated favorable physicochemical properties, stability, spreadability, and controlled release of AmB. The in vivo findings highlight its promising antileishmanial activity and support the potential of AmB-loaded bigels as a therapeutic alternative for ATL.
{"title":"Amphotericin B-Loaded Bigel: Characterization and in vivo Antileishmanial Evaluation in BALB/c Mice Infected with Leishmania amazonensis","authors":"Rosilene Ribeiro de Sousa, Matheus Oliveira do Nascimento, Leandro Josuel da Costa Santos, Francisco Gesley de Sousa Abreu, André Luiz Pinheiro de Moura, Daniele Costa Lopes, Karla Germana dos Reis Bacelar, Rita de Cássia Vianna de Carvalho, Paulline Paiva Mendes de Souza Leal, Charllyton Luis Sena da Costa, Vitória de Cássia Coelho Rodrigues, Fernando Aécio de Amorim Carvalho, Michel Muálem de Moraes Alves, André Luis Menezes Carvalho","doi":"10.1208/s12249-025-03303-4","DOIUrl":"10.1208/s12249-025-03303-4","url":null,"abstract":"<div><p>American Tegumentary Leishmaniasis (ATL) is a zoonotic disease characterized by polymorphic cutaneous and mucosal manifestations, caused by protozoa of the genus <i>Leishmania</i> and transmitted through the bite of sandflies. Current treatment relies on pharmacotherapy with drugs such as amphotericin B (AmB), which is limited by adverse effects. Novel topical formulations of AmB, including bigels, have been investigated as alternatives for ATL therapy, aiming to achieve local efficacy with reduced toxicity and lower cost. This study sought to develop and characterize an AmB loaded-bigel for topical application and to evaluate its <i>in vivo</i> antileishmanial activity. The formulations were characterized by organoleptic analysis, pH, stability, oil retention capacity, swelling, spreadability, and texture profile. <i>In vitro</i> drug release and skin permeation were assessed using Franz diffusion cells and murine skin, while the ocular irritation potential was evaluated through the HET-CAM assay. <i>In vivo</i> efficacy was tested in BALB/c mice infected with <i>Leishmania amazonensis</i>, monitoring lesion progression and parasite burden. Treatment with the AmB loaded-bigel resulted in a 74.1% reduction in parasite load. Overall, the bigel demonstrated favorable physicochemical properties, stability, spreadability, and controlled release of AmB. The <i>in vivo</i> findings highlight its promising antileishmanial activity and support the potential of AmB-loaded bigels as a therapeutic alternative for ATL.</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":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930346","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}
Pub Date : 2026-01-08DOI: 10.1208/s12249-025-03318-x
B. J. Navarro, L. Kakuda, P. M. B. G. Maia Campos
Post-inflammatory hyperpigmentation (PIH) is a prevalent dermatological condition arising from inflammatory processes that significantly impacts quality of life. Natural alternatives to conventional treatments are increasingly sought to minimize adverse effects while maintaining efficacy. This study aimed to develop and evaluate an innovative oil-in-serum formulation containing olive extract standardized in hydroxytyrosol (HT) for PIH treatment, assessing its stability, sensory properties, and clinical efficacy. Two complementary formulations were developed: a hydroxyethylcellulose-based gel (with/without 0.1% olive extract containing 20% HT) and an olive oil-based formulation. Stability tests, texture analysis, sensory evaluation and clinical efficacy analysis in participants with PIH were conducted. Overall, the formulations were stable and showed favorable sensory properties. The oil-in-serum system exhibited enhanced spreadability, hydration perception, and reduced stickiness compared to individual components. After 45 days of application, the formulation with HT increased stratum corneum water content and reduced transepidermal water loss (TEWL), indicating improved skin barrier function. A significant reduction in color difference between lesional and perilesional areas was observed in high-resolution imaging analysis, showing a reduction in the PIH. Participants reported enhanced skin hydration and reduced dark spots, which corroborate the instrumental measurements results. Finally, the oil-in-serum formulation with olive extract standardized in HT proved effective for PIH treatment, combining excellent sensory properties with clinical efficacy in improving skin hydration, barrier function, and hyperpigmentation control.
{"title":"Development, Stability, and Clinical Efficacy of an Oil-in-Serum Formulation with Olive Extract Standardized in Hydroxytyrosol for Post-Inflammatory Hyperpigmentation Treatment","authors":"B. J. Navarro, L. Kakuda, P. M. B. G. Maia Campos","doi":"10.1208/s12249-025-03318-x","DOIUrl":"10.1208/s12249-025-03318-x","url":null,"abstract":"<div><p>Post-inflammatory hyperpigmentation (PIH) is a prevalent dermatological condition arising from inflammatory processes that significantly impacts quality of life. Natural alternatives to conventional treatments are increasingly sought to minimize adverse effects while maintaining efficacy. This study aimed to develop and evaluate an innovative oil-in-serum formulation containing olive extract standardized in hydroxytyrosol (HT) for PIH treatment, assessing its stability, sensory properties, and clinical efficacy. Two complementary formulations were developed: a hydroxyethylcellulose-based gel (with/without 0.1% olive extract containing 20% HT) and an olive oil-based formulation. Stability tests, texture analysis, sensory evaluation and clinical efficacy analysis in participants with PIH were conducted. Overall, the formulations were stable and showed favorable sensory properties. The oil-in-serum system exhibited enhanced spreadability, hydration perception, and reduced stickiness compared to individual components. After 45 days of application, the formulation with HT increased stratum corneum water content and reduced transepidermal water loss (TEWL), indicating improved skin barrier function. A significant reduction in color difference between lesional and perilesional areas was observed in high-resolution imaging analysis, showing a reduction in the PIH. Participants reported enhanced skin hydration and reduced dark spots, which corroborate the instrumental measurements results. Finally, the oil-in-serum formulation with olive extract standardized in HT proved effective for PIH treatment, combining excellent sensory properties with clinical efficacy in improving skin hydration, barrier function, and hyperpigmentation control.\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":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930542","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}
Pub Date : 2026-01-08DOI: 10.1208/s12249-025-03313-2
Namdeo R. Jadhav, Sonali R. Yede, Asha S. Jadhav, Megha N. Mane, Prathamesh S. Patil, Suhas S. Mohite
Nanostructured lipid carriers (NLCs) have been researched extensively for nose-to-brain drug delivery but are often constrained by low drug solubility, limited payload, and poor permeability. Herein, we have developed Hybrid NLCs (Liquid lipid replaced with bioionic liquid) to enhance drug solubility, permeability, payload, and nose-to-brain bioavailability of Tetrabenazine hydrochloride (TBZ), a BCS-class IV drug. The formulation and optimization of the Hybrid-NLCs was carried out using a central composite design, followed by loading into an in-situ gel. The optimized TBZ Hybrid-NLCs demonstrated a particle size of 149.84 ± 0.73 nm, PDI 0.33 ± 0.01, zeta potential -38.96 ± 0.09 mV, and % Entrapment efficiency 97.65 ± 0.70%. The % Drug loading of TBZ in Hybrid-NLCs was significantly higher (34.4 ± 0.98%) compared to 28.2 ± 0.54% in conventional or Plain NLCs, reflecting superior drug-loading (p < 0.05). Comparative in-vitro and ex-vivo drug release studies revealed improved TBZ release (74.22 ± 0.20% in-vitro, and 74.73 ± 0.64% ex-vivo) from Hybrid-NLCs, compared to the Plain-NLCs (66.44 ± 0.21% in-vitro and 61.18 ± 0.39% ex-vivo). Intranasal administration of TBZ-loaded-Hybrid-NLC gels in Wistar rats showed Cmax 7.87 ± 0.80 µg/ml and Tmax 5–6 h in brain tissue, outperforming (Plain-NLC), achieving Cmax 6.32 ± 0.30 µg/ml and a similar Tmax. Conclusively, the nose-to-brain delivery of TBZ-loaded Hybrid-NLCs gel significantly enhanced TBZ bioavailability to the brain, 1.51-fold over Plain-NLCs gel. Findings underscored Hybrid-NLCs as a promising non-invasive strategy for enhancing the bioavailability of BCS class IV drugs via nose to brain delivery, prospective in the treatment of neurological diseases/disorders.
{"title":"Optimization of Ionic Liquid Based NLC for Nose-To-Brain Delivery of Tetrabenazine Hydrochloride","authors":"Namdeo R. Jadhav, Sonali R. Yede, Asha S. Jadhav, Megha N. Mane, Prathamesh S. Patil, Suhas S. Mohite","doi":"10.1208/s12249-025-03313-2","DOIUrl":"10.1208/s12249-025-03313-2","url":null,"abstract":"<div><p>Nanostructured lipid carriers (NLCs) have been researched extensively for nose-to-brain drug delivery but are often constrained by low drug solubility, limited payload, and poor permeability. Herein, we have developed Hybrid NLCs (Liquid lipid replaced with bioionic liquid) to enhance drug solubility, permeability, payload, and nose-to-brain bioavailability of Tetrabenazine hydrochloride (TBZ), a BCS-class IV drug. The formulation and optimization of the Hybrid-NLCs was carried out using a central composite design, followed by loading into an <i>in-situ</i> gel. The optimized TBZ Hybrid-NLCs demonstrated a particle size of 149.84 ± 0.73 nm, PDI 0.33 ± 0.01, zeta potential -38.96 ± 0.09 mV, and % Entrapment efficiency 97.65 ± 0.70%. The % Drug loading of TBZ in Hybrid-NLCs was significantly higher (34.4 ± 0.98%) compared to 28.2 ± 0.54% in conventional or Plain NLCs, reflecting superior drug-loading (p < 0.05). Comparative <i>in-vitro</i> and <i>ex-vivo</i> drug release studies revealed improved TBZ release (74.22 ± 0.20% <i>in-vitro</i>, and 74.73 ± 0.64% <i>ex-vivo</i>) from Hybrid-NLCs, compared to the Plain-NLCs (66.44 ± 0.21% <i>in-vitro</i> and 61.18 ± 0.39% <i>ex-vivo</i>). Intranasal administration of TBZ-loaded-Hybrid-NLC gels in Wistar rats showed C<sub>max</sub> 7.87 ± 0.80 µg/ml and T<sub>max</sub> 5–6 h in brain tissue, outperforming (Plain-NLC), achieving C<sub>max</sub> 6.32 ± 0.30 µg/ml and a similar T<sub>max</sub>. Conclusively, the nose-to-brain delivery of TBZ-loaded Hybrid-NLCs gel significantly enhanced TBZ bioavailability to the brain, 1.51-fold over Plain-NLCs gel. Findings underscored Hybrid-NLCs as a promising non-invasive strategy for enhancing the bioavailability of BCS class IV drugs via nose to brain delivery, prospective in the treatment of neurological diseases/disorders.\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":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930538","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}
Pub Date : 2026-01-08DOI: 10.1208/s12249-025-03294-2
Manjusha Annaji, Ishwor Poudel, Nur Mita, Chu Zhang, Humaira Yeasmin, Seungjong Lee, Peter Panizzi, Robert D. Arnold, Amal Kaddoumi, Nima Shamsaei, Byron Farnum, Oladiran Fasina, R. Jayachandra Babu
Implant failures in orthopedic surgeries can occur due to inflammation, poor osteointegration, and biofilm formation. The local delivery of anti-inflammatory drugs is one of the potential solutions to address orthopedic implant failures caused by extensive inflammation, poor osteointegration, and biofilm formation. This study utilized a simple spray coating technique to deposit multilayer coatings of the anti-inflammatory drug meloxicam and PLGA on 3D printed 316L stainless steel implants. The implants were evaluated for their drug content, drug-polymer miscibility, static contact angle, corrosion resistance, in vitro release, cell adhesion, cell proliferation, and bacterial adhesion studies. The coatings aimed to improve osteointegration and reduce biofilm formation. The drug release studies demonstrated an initial burst release accompanied by sustained release for more than 30 days. The meloxicam-PLGA coated implants showed higher resistance to pitting corrosion, improved adhesion, and proliferation of human U2OS cells in comparison to uncoated implants. In addition, results from cell cytotoxicity studies confirmed that all the coatings are biocompatible and safe for in vivo application. The meloxicam-PLGA coated implants were also found to have significantly lower bacterial adhesion and biofilm formation compared to uncoated implants for both S. aureus (p < 0.01) and S. pseudintermedius (p < 0.01). The multilayer coatings developed in this study have the potential to improve adhesion at the implant-bone interface and thus might prevent implant rejections in patients undergoing orthopedic surgery. Moreover, this method can be applied to other drugs and polymers to address the issues related to implant failure, pain management, and surgical site infections.
{"title":"Meloxicam Eluting 3D Printed 316L Stainless Steel Implants for Targeted Delivery in Bone Fixation Surgeries","authors":"Manjusha Annaji, Ishwor Poudel, Nur Mita, Chu Zhang, Humaira Yeasmin, Seungjong Lee, Peter Panizzi, Robert D. Arnold, Amal Kaddoumi, Nima Shamsaei, Byron Farnum, Oladiran Fasina, R. Jayachandra Babu","doi":"10.1208/s12249-025-03294-2","DOIUrl":"10.1208/s12249-025-03294-2","url":null,"abstract":"<div><p>Implant failures in orthopedic surgeries can occur due to inflammation, poor osteointegration, and biofilm formation. The local delivery of anti-inflammatory drugs is one of the potential solutions to address orthopedic implant failures caused by extensive inflammation, poor osteointegration, and biofilm formation. This study utilized a simple spray coating technique to deposit multilayer coatings of the anti-inflammatory drug meloxicam and PLGA on 3D printed 316L stainless steel implants. The implants were evaluated for their drug content, drug-polymer miscibility, static contact angle, corrosion resistance, <i>in vitro</i> release, cell adhesion, cell proliferation, and bacterial adhesion studies. The coatings aimed to improve osteointegration and reduce biofilm formation. The drug release studies demonstrated an initial burst release accompanied by sustained release for more than 30 days. The meloxicam-PLGA coated implants showed higher resistance to pitting corrosion, improved adhesion, and proliferation of human U2OS cells in comparison to uncoated implants. In addition, results from cell cytotoxicity studies confirmed that all the coatings are biocompatible and safe for <i>in vivo</i> application. The meloxicam-PLGA coated implants were also found to have significantly lower bacterial adhesion and biofilm formation compared to uncoated implants for both <i>S. aureus</i> (<i>p</i> < 0.01) and <i>S. pseudintermedius</i> (<i>p</i> < 0.01). The multilayer coatings developed in this study have the potential to improve adhesion at the implant-bone interface and thus might prevent implant rejections in patients undergoing orthopedic surgery. Moreover, this method can be applied to other drugs and polymers to address the issues related to implant failure, pain management, and surgical site infections.</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":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03294-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930539","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}
Pub Date : 2026-01-08DOI: 10.1208/s12249-025-03266-6
Qian Ye, Sheng Wang, Zhaoyang Zhang
Recently, pharmaceutical cocrystal technology has garnered considerable global attention because of its innovativeness and environmental sustainability. This technology effectively enhances the bioavailability of poorly soluble drugs and optimizes their physicochemical and biological properties. Considering the pivotal role of cocrystal screening in improving drug bioavailability, herein, we develop a comprehensive framework for understanding the definition, screening, key characteristics, and applications of drug cocrystals in contemporary drug development. We discuss a series of innovative and efficient screening methods, such as high-throughput computational screening, artificial intelligence screening, and Raman spectroscopy, focusing particularly on the application of machine learning (ML) algorithms. Such algorithms can analyze large volumes of physicochemical data for virtual cocrystal screening and solubility prediction. Compared with traditional experimental screening methods—such as X-ray diffraction, thermal analysis (TA), and high-performance liquid chromatography (HPLC), ML models can manage high workload, address gaps in screening, and facilitate accurate solubility prediction. By using ML models, researchers can narrow the experimental scope and accelerate the discovery and development of novel drug cocrystals. This approach holds promise for enhancing drug efficacy, reducing adverse reactions, and improving patient compliance. Future studies should integrate experimental and virtual screening methods to enhance the efficiency and accuracy of cocrystal selection.
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Pub Date : 2025-12-18DOI: 10.1208/s12249-025-03268-4
Ajay J. Khopade, Malay D. Shah, Bhushan S. Borole, Bharat Patel, Bharat Pateliya, Vinod Burade
This study evaluates the safety, tolerability, pharmacokinetics, and tissue distribution of paclitaxel injection concentrate for nanodispersion (PICN), either as standalone treatment or in comparison with Abraxane® (AbX) and Oncotaxel (OtX, generic formulation of Taxol® from Sun Pharma). In vitro cytotoxicity was assessed in—HT-29, PC-3, SKOV3 and NCI H522 human cancer cell lines. Single- and multiple-dose toxicity studies were conducted in rodents evaluating clinical signs, hematology, histopathology, and organ-specific toxicity. Pharmacokinetic studies were performed in rats analyzing Paclitaxel (PtX) concentrations by LC–MS/MS. PICN demonstrated comparable in vitro cytotoxicity to OtX. Single- and repeat-dose toxicity studies revealed that PICN has similar toxicity profile with AbX, including reversible lymphoid depletion and irreversible testicular toxicity at higher doses. Known PtX class effects, myelosuppression and neuropathy was observed in both PICN and reference groups; with less pronounced effects in females. PICN (at 10 mg/kg) produced a lower reduction in pain threshold (~ 22%) compared to OtX (~ 43%), suggesting a reduced potential for neurotoxicity. PICN showed no local irritation following IV administration and no hemolytic potential in-vitro. It exhibited dose-proportional increases in Cmax and AUC0–inf across 5–20 mg/kg, with pharmacokinetic parameters comparable to AbX. Red blood cell (RBC) partitioning studies indicated balanced distribution for PICN compared to OtX, and slightly lower RBC exposure than AbX. PICN also demonstrated moderate PtX distributions with concentrations higher than AbX but substantially lower than OtX in various tissues. Collectively, these results support PICN as a promising alternative, combining favorable safety and comparable pharmacokinetics.
{"title":"Preclinical Toxicity and Pharmacokinetic Evaluation of Paclitaxel Nanodispersion","authors":"Ajay J. Khopade, Malay D. Shah, Bhushan S. Borole, Bharat Patel, Bharat Pateliya, Vinod Burade","doi":"10.1208/s12249-025-03268-4","DOIUrl":"10.1208/s12249-025-03268-4","url":null,"abstract":"<div><p>This study evaluates the safety, tolerability, pharmacokinetics, and tissue distribution of paclitaxel injection concentrate for nanodispersion (PICN), either as standalone treatment or in comparison with Abraxane® (AbX) and Oncotaxel (OtX, generic formulation of Taxol® from Sun Pharma). <i>In vitro</i> cytotoxicity was assessed in—HT-29, PC-3, SKOV3 and NCI H522 human cancer cell lines. Single- and multiple-dose toxicity studies were conducted in rodents evaluating clinical signs, hematology, histopathology, and organ-specific toxicity. Pharmacokinetic studies were performed in rats analyzing Paclitaxel (PtX) concentrations by LC–MS/MS. PICN demonstrated comparable <i>in vitro</i> cytotoxicity to OtX. Single- and repeat-dose toxicity studies revealed that PICN has similar toxicity profile with AbX, including reversible lymphoid depletion and irreversible testicular toxicity at higher doses. Known PtX class effects, myelosuppression and neuropathy was observed in both PICN and reference groups; with less pronounced effects in females. PICN (at 10 mg/kg) produced a lower reduction in pain threshold (~ 22%) compared to OtX (~ 43%), suggesting a reduced potential for neurotoxicity. PICN showed no local irritation following IV administration and no hemolytic potential in-vitro. It exhibited dose-proportional increases in C<sub>max</sub> and AUC<sub>0–inf</sub> across 5–20 mg/kg, with pharmacokinetic parameters comparable to AbX. Red blood cell (RBC) partitioning studies indicated balanced distribution for PICN compared to OtX, and slightly lower RBC exposure than AbX. PICN also demonstrated moderate PtX distributions with concentrations higher than AbX but substantially lower than OtX in various tissues. Collectively, these results support PICN as a promising alternative, combining favorable safety and comparable pharmacokinetics.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772881","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}
Pub Date : 2025-12-17DOI: 10.1208/s12249-025-03287-1
Andrés Felipe Pérez Palacios, Jorge Alexis Medina Parra, Daniel Santiago Córdoba Velasco, Diana Carolina Zona Rubio, Izabel Almeida Alves, Diana Marcela Aragón Novoa
Poor aqueous solubility is a major barrier in drug development, affecting dissolution, absorption, and systemic bioavailability. Nearly 40% of approved drugs and up to 90% of new chemical entities face this limitation, resulting in therapeutic inefficacy and costly clinical development. This study reviewed patents published between 2015 and 2024 that describe technological strategies to enhance drug solubility and bioavailability, aiming to identify innovation trends and their pharmaceutical impact. A structured search was conducted in the Espacenet database using the keywords “bioavailability” and “solubility” under the IPC code A61K. From 98,111 initial results, duplicates, language restrictions, and patents related to cosmetics, nutrition, or veterinary products were excluded, yielding 29 eligible documents. Extracted data included applicant country, therapeutic indication, BCS classification, formulation approach, manufacturing method, and available in vivo pharmacokinetic results. Descriptive analysis was performed using R software. China led patent registrations (55%), followed by the USA (17%). Patent filings increased steadily from 2016–2020, decreased during the COVID-19 pandemic, and recovered after 2021. Most drugs belonged to BCS Class II (76%), reflecting high permeability but poor solubility. The main strategies included particle size reduction, solid dispersions, self-emulsifying drug delivery systems, cyclodextrin inclusion complexes, and advanced crystallization techniques. When reported, pharmacokinetic data showed significant improvements in Cmax and AUC; however, only 58% of patents included in vivo studies. Overall, patents reveal robust innovation aimed at overcoming solubility challenges.
{"title":"New Strategies to Improve Drug Solubility and Its Impact on Bioavailability: A Patent Review (2015–2024)","authors":"Andrés Felipe Pérez Palacios, Jorge Alexis Medina Parra, Daniel Santiago Córdoba Velasco, Diana Carolina Zona Rubio, Izabel Almeida Alves, Diana Marcela Aragón Novoa","doi":"10.1208/s12249-025-03287-1","DOIUrl":"10.1208/s12249-025-03287-1","url":null,"abstract":"<div><p>Poor aqueous solubility is a major barrier in drug development, affecting dissolution, absorption, and systemic bioavailability. Nearly 40% of approved drugs and up to 90% of new chemical entities face this limitation, resulting in therapeutic inefficacy and costly clinical development. This study reviewed patents published between 2015 and 2024 that describe technological strategies to enhance drug solubility and bioavailability, aiming to identify innovation trends and their pharmaceutical impact. A structured search was conducted in the Espacenet database using the keywords “bioavailability” and “solubility” under the IPC code A61K. From 98,111 initial results, duplicates, language restrictions, and patents related to cosmetics, nutrition, or veterinary products were excluded, yielding 29 eligible documents. Extracted data included applicant country, therapeutic indication, BCS classification, formulation approach, manufacturing method, and available in vivo pharmacokinetic results. Descriptive analysis was performed using R software. China led patent registrations (55%), followed by the USA (17%). Patent filings increased steadily from 2016–2020, decreased during the COVID-19 pandemic, and recovered after 2021. Most drugs belonged to BCS Class II (76%), reflecting high permeability but poor solubility. The main strategies included particle size reduction, solid dispersions, self-emulsifying drug delivery systems, cyclodextrin inclusion complexes, and advanced crystallization techniques. When reported, pharmacokinetic data showed significant improvements in Cmax and AUC; however, only 58% of patents included in vivo studies. Overall, patents reveal robust innovation aimed at overcoming solubility challenges.\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":"27 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145772934","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}
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