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1.
J Microencapsul ; 40(5): 366-383, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37129532

RESUMEN

Tizanidine HCl (TH) is used as first-line therapy for the treatment of muscular spasm. The intranasal cubosomal delivery system of TH for site-specific delivery, i.e. CNS was developed. Cubosomes of TH were prepared using glyceryl monooleate (GMO) as a lipid, poloxamer 407 as stabiliser, and ethanol and polyethylene glycol 200 as co-solvent. Optimised cubosomes of TH were characterised for vesicle size, zeta potential, % drug entrapment, and mucin binding efficiency, which were found to be 50.22 nm, -6.39 mV, 69.28%, and 42.12%. It is also evaluated for CRYO-FESEM, CRYO-TEM, SAXS, residual solvent content, and in vitro drug release. Ex vivo permeation was also conducted at 7.4 and it indicates that almost 93.66% drug was diffused from a formulation in 6 h. Histopathological study of the optimised TH cubosomes suggests that the prepared formulation is non-toxic to the nasal mucosa. Pharmacokinetic and brain distribution study indicates targeted action of the formulated TH cubosomes.


Asunto(s)
Encéfalo , Poloxámero , Dispersión del Ángulo Pequeño , Geles/química , Difracción de Rayos X , Encéfalo/metabolismo , Administración Intranasal , Poloxámero/química , Tamaño de la Partícula
2.
AAPS PharmSciTech ; 22(7): 236, 2021 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-34535843

RESUMEN

Risedronate sodium (RS) is used in osteoporosis for bone reabsorption. It is a BCS class III drug having poor oral bioavailability (<0.63%) due to low permeability. In the present study, RS-loaded chitosan nanoparticles were developed to increase oral bioavailability and evaluated for various parameters. The DSC study indicated compatibility of RS with excipients in their physical mixture. The nanoparticles were prepared by ionotropic gelation technique and lyophilized. The optimized batch (RS-CNs) was found to have particles of size 268.7 nm and zeta potential of 24.9 mV. The TEM image of RS-CNs revealed discrete spherical particles. Angle of repose of 27.02 indicates good flow property of nanoparticles. FT-IR spectra of RS-CNs showed characteristic peaks of RS indicating compatibility of RS with the excipients. The mucin binding efficiency of RS-CNs was obtained as 63.42%. The in vitro release study of RS indicated controlled delivery from RS-CNs over 22 h. The release mechanism was found to be diffusion- and erosion-controlled release. Ex vivo study using rat intestine revealed faster permeation of 32.78% in 6 h from RS-CNs compared to plain drug solution. In vivo pharmacokinetic study in rats showed increased Cmax (1.8 fold) from RS-CNs compared to marketed formulation. The relative bioavailability of 193% from RS-CNs indicated significant enhancement in bioavailability upon nanoparticle formulation. The RS-CNs were found to be stable at room and refrigerated conditions. In conclusion, developed RS-loaded chitosan nanoparticles seem to be a promising approach to increase oral bioavailability and can avoid upper GI tract side effects.


Asunto(s)
Quitosano , Nanopartículas , Ácido Risedrónico , Administración Oral , Animales , Disponibilidad Biológica , Portadores de Fármacos , Tamaño de la Partícula , Ratas , Espectroscopía Infrarroja por Transformada de Fourier
3.
AAPS PharmSciTech ; 21(5): 182, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32613377

RESUMEN

The aim of the present investigation was to formulate self-microemulsifying drug delivery system (SMEDDS) tablets to enhance the oral bioavailability of tizanidine hydrochloride. SMEDDS was prepared by using Capmul G as the oil phase, Tween 20 as the surfactant, and propylene glycol as the co-surfactant. The optimized formulation was characterized by dilution test, % transmittance, thermodynamic stability, dye solubility, assay, globule size, zeta potential, and TEM. A dye solubility test confirmed the formation of o/w microemulsion. Optimized formulation of SMEDDS had a drug content of 98 ± 0.75% (3.2± 0.3 mg) and droplet size of 96.61 ± 2.3 nm. Dilution and centrifugation tests indicated the physical stability of the formulation. The optimized SMEDDS was mixed with Neusilin as adsorbent, microcrystalline cellulose as diluent, and magnesium stearate as flow promoter, and compressed into tablets. The prepared tablets passed the tests of weight variation, hardness, friability, and assay. In vitro dissolution test indicated sustained release of tizanidine hydrochloride from the SMEDDS tablet for a period of 4 h. In vivo pharmacokinetic studies performed on male New Zealand rabbits showed a 4.61-fold increase in bioavailability compared with the marketed formulation. Thus, the developed SMEDDS tablet proved to be capable of enhancing oral bioavailability of tizanidine hydrochloride. Graphical abstract.


Asunto(s)
Clonidina/análogos & derivados , Emulsiones/química , Administración Oral , Animales , Disponibilidad Biológica , Química Farmacéutica , Clonidina/administración & dosificación , Clonidina/química , Clonidina/farmacocinética , Técnicas In Vitro , Masculino , Conejos , Solubilidad , Comprimidos
4.
Pulm Pharmacol Ther ; 49: 36-45, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29337265

RESUMEN

Vinorelbine Tartrate (VLB) is the first line chemotherapeutic agent for treatment of Non-Small Cell Lung Cancer, whose non-specific distribution causes unwanted side effects. The aim of the present investigation was to formulate VLB loaded spherulites intended for targeting the lung. Spherulites were composed of Soyabean Phosphatidylcholine (SPC), Cholesterol (Chol), Potassium oleate and Mannitol. Lipid film prepared using SPC, Chol and Potassium oleate, was dispersed in aqueous phase comprising Mannitol and VLB, followed by controlled shearing and extrusion. PEGylated Spherulites were prepared by incorporating 1,2-distearoyl-sn-glycero-3 phosphatidylethanolamine-N-[methoxy poly (ethylene glycol)] (DSPE-PEG 2000) in the lipid phase. Vesicles were characterized for size, entrapment efficiency and drug release. In vitro cell cytotoxicity and apoptosis study were performed on A549 cell line. Radiolabeling of VLB was performed by direct labeling with reduced technetium-99m. Binding affinity of 99mTc- labelled complexes was assessed by diethylenetriaminepenta acetic acid (DTPA) challenge test. Biodistribution study was done in Sprague Dawley rats. Dynamic light scattering and Transmission electron micrographs confirmed that PEGylated and non-PEGylated Spherulites were discrete, spherical and exhibited the size range of 120-130 nm. Non-PEGylated and PEGylated Spherulites had an entrapment efficiency of 95.65% and 94.2% respectively. In vitro drug release study indicated VLB plain drug solution diffused completely within 24 h, however, Non-PEGylated and PEGylated Spherulites showed similar release pattern till 48 h. Results of cell line study showed that cells treated with VLB loaded Spherulites showed more cytotoxicity and underwent high degree of apoptosis at lower concentration compared to the VLB solution. Radiolabeled complex was stable in saline and serum, further, DTPA challenge study ensured the high binding strength. Gamma Scintigraphy displayed that PEGylated Spherulites were localized within lungs at higher concentration than non-PEGylated followed by plain drug.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Sistemas de Liberación de Medicamentos , Pulmón/metabolismo , Vinorelbina/administración & dosificación , Células A549 , Animales , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Portadores de Fármacos/química , Liberación de Fármacos , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Tamaño de la Partícula , Fosfatidiletanolaminas/química , Polietilenglicoles/química , Cintigrafía/métodos , Ratas , Ratas Sprague-Dawley , Tecnecio/administración & dosificación , Distribución Tisular , Vinorelbina/farmacocinética , Vinorelbina/farmacología
5.
AAPS PharmSciTech ; 19(2): 648-660, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28948564

RESUMEN

Darunavir has a low oral bioavailability (37%) due to its lipophilic nature, metabolism by cytochrome P450 enzymes and P-gp efflux. Lipid nanoparticles were prepared in order to overcome its low bioavailability and to increase the binding efficacy of delivery system to the lymphoid system. Darunavir-loaded lipid nanoparticles were prepared using high-pressure homogenization technique. Hydrogenated castor oil was used as lipid. Peptide, having affinity for CD4 receptors, was grafted onto the surface of nanoparticles. The nanoparticles were evaluated for various parameters. The nanoparticles showed size of less than 200 nm, zeta potential of - 35.45 mV, and a high drug entrapment efficiency (90%). 73.12% peptide was found conjugated to nanoparticles as studied using standard BSA calibration plot. Permeability of nanoparticles in Caco-2 cells was increased by 4-fold in comparison to plain drug suspension. Confocal microscopic study revealed that the nanoparticles showed higher uptake in HIV host cells (Molt-4 cells were taken as model containing CD4 receptors) as compared to non-CD4 receptor bearing Caco-2 cells. In vivo pharmacokinetic in rats showed 569% relative increase in bioavailability of darunavir as compared to plain drug suspension. The biodistribution study revealed that peptide-grafted nanoparticles showed higher uptake in various organs (also in HIV reservoir organs namely the spleen and brain) except the liver compared to non-peptide-grafted nanoparticles. The prepared nanoparticles resulted in increased binding with the HIV host cells and thus could be promising carrier in active targeting of the drugs to the HIV reservoir.


Asunto(s)
Darunavir/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Inhibidores de la Proteasa del VIH/administración & dosificación , Nanopartículas/administración & dosificación , Secuencia de Aminoácidos , Animales , Disponibilidad Biológica , Células CACO-2 , Darunavir/metabolismo , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Inhibidores de la Proteasa del VIH/metabolismo , Humanos , Lípidos , Masculino , Nanopartículas/metabolismo , Tamaño de la Partícula , Permeabilidad , Ratas , Ratas Wistar , Distribución Tisular/efectos de los fármacos , Distribución Tisular/fisiología
6.
J Microencapsul ; 34(7): 644-658, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28862072

RESUMEN

The aim of the present investigation was to formulate tapentadol hydrochloride-loaded chitosan nanoparticles (CS-NPs) for nose to brain delivery. Chitosan nanoparticles were prepared using ionotropic gelation technique. Optimisation of the formulation and process parameters was done using Box-Behnken Design. The entrapment efficiency, drug loading, Z-average size and zeta potential of the optimised batch were 63.49 ± 1.61%, 17.25 ± 1.38%w/w, 201.2 ± 1.5 nm and +49.3 mV, respectively. In-vitro release study showed 84.04 ± 1.53% drug release after 28 h, while ex vivo studies indicated higher permeation of CS-NPs through nasal mucosa. The nanoparticles exhibited good mucoadhesiveness, haemocompatibility and safety as evidenced by histopathology. The results of the pharmacodynamic study revealed prolongation of the analgesic activity. The intranasal instillation of CS-NPs resulted in the higher concentrations in brain compared to the drug solution and intravenous administration of CS-NPs. In a nutshell, intranasal administration of tapentadol hydrochloride-loaded CS-NPs is a promising approach for effective pain management.


Asunto(s)
Quitosano/química , Nanopartículas , Fenoles/administración & dosificación , Administración Intranasal , Animales , Composición de Medicamentos , Femenino , Cabras , Microscopía Electrónica de Rastreo , Fenoles/metabolismo , Fenoles/farmacocinética , Ratas , Ratas Sprague-Dawley , Receptores Opioides mu/metabolismo , Tapentadol
7.
J Microencapsul ; 34(7): 623-634, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28845737

RESUMEN

Gemcitabine hydrochloride (GCH) is drug of choice for treatment of non-small cell lung cancer. This project aims to formulate GCH-loaded spherulites for lung targeting using soyabean phosphatidylcholine, cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000]. Vesicles were characterised for size, entrapment efficiency, drug release and in vitro cytotoxicity. Radiolabelling of GCH was done using reduced technetium-99 m to study biodistribution in Sprague-Dawley rats. Discrete and spherical, PEGylated and non-PEGylated spherulites with an average size of 200 nm as seen in transmission electron microscopy had an entrapment efficiency of 76.28% and 77.42%, respectively. PEGylated spherulites showed sustained release followed by non-PEGylated and plain drug. GCH spherulites exhibited significantly higher cytotoxicity and apoptosis at reduced concentration than GCH solution. The radiolabelled complex showed high binding and radiolabelling efficiency. Gamma scintigraphy showed that GCH-loaded PEGylated spherulites were able to localise within lungs in higher concentration than non-PEGylated followed by plain drug.


Asunto(s)
Antimetabolitos Antineoplásicos/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/metabolismo , Compuestos de Organotecnecio/farmacocinética , Cintigrafía/métodos , Células A549 , Animales , Antimetabolitos Antineoplásicos/química , Desoxicitidina/química , Desoxicitidina/farmacocinética , Estabilidad de Medicamentos , Humanos , Técnicas In Vitro , Microscopía Electrónica de Transmisión , Compuestos de Organotecnecio/química , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Gemcitabina
8.
J Microencapsul ; 33(7): 669-678, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27701988

RESUMEN

The present investigation aimed to study the effect of particle size of solid lipid nanoparticles (SLNs) on oral bioavailability of darunavir. High pressure homogenisation technique was used to prepare SLNs. Three different sized SLNs loaded with darunavir were developed with mean particle sizes of around 100 nm, 200 nm and 500 nm, respectively. The in vivo pharmacokinetics in rats showed a significant increase in oral bioavailability of darunavir from all the three formulations in comparison to plain drug suspension and reference tablet. The results revealed insignificant difference between SLNs of 100 and 200 nm and these had significantly higher bioavailability in comparison to SLNs of 500 nm. However, more number of homogenisation cycles is required for obtaining 100 nm and thus we selected 200 nm as an optimum size for oral bioavailability enhancement of darunavir. The optimised SLN formulation was stable for a period of 6 months at 25 ± 2 °C/60 ± 5% relative humidity (RH).


Asunto(s)
Darunavir , Portadores de Fármacos , Nanopartículas , Dolor/tratamiento farmacológico , Administración Oral , Animales , Darunavir/química , Darunavir/farmacocinética , Darunavir/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Lípidos , Masculino , Nanopartículas/química , Nanopartículas/ultraestructura , Dolor/metabolismo , Tamaño de la Partícula , Ratas , Ratas Wistar
9.
AAPS PharmSciTech ; 17(5): 1248-60, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26677859

RESUMEN

The present study aimed to prepare, optimize, and evaluate Tapentadol hydrochloride controlled porosity osmotic pump (CPOP) and to achieve the drug release at nearly zero-order. The CPOP was prepared by the coating of polymers (Eudragit RSPO and RLPO) on a directly compressed core tablet. A Box-behnken experimental design was applied to optimize the parameters for CPOP. The optimized batch was characterized for in vitro drug release study, effect of pH, osmolarity and agitation intensity, and surface morphology and stability study. In vivo pharmacokinetic studies were performed on New Zealand white rabbits for CPOP and marketed tablet. All the batches showed a drug release ranging from 29.87 to 56.92% after 12 h; and from 59.64 to 99.96% after 24 h. There was no change in the drug release pattern at different pH and agitation intensities. The drug release was found to decrease with increasing osmolarity of dissolution media.An in vivo study showed a higher mean residence time, area under the curve, and biological half-life (T 1/2) than the marketed tablet with low rate of elimination (Ke) and a 2.35-fold increase in relative bioavailability. The result showed that the amounts of sodium chloride and PEG 400 were contributing positively while the number of coats was negatively affecting the drug release. The drug release was found to be independent of physiological conditions. The stability testing showed that the prepared CPOP was stable for 3 months at accelerated conditions. The prepared CPOP was found to deliver Tapentadol hydrochloride at zero-order for up to 24 h.


Asunto(s)
Preparaciones de Acción Retardada/química , Fenoles/química , Animales , Disponibilidad Biológica , Preparaciones de Acción Retardada/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Excipientes/química , Semivida , Cinética , Ósmosis , Fenoles/metabolismo , Polietilenglicoles/química , Polímeros/química , Porosidad , Conejos , Cloruro de Sodio/química , Solubilidad , Comprimidos/química , Comprimidos/metabolismo , Tapentadol
10.
J Microencapsul ; 32(6): 559-69, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26333939

RESUMEN

Itraconazole (ITR), an antifungal agent has poor bioavailability due to low aqueous solubility. The present investigation aimed at development of ITR nanoemulsion to enhance its oral bioavailability. ITR nanoemulsion was prepared using Capmul MCM C8 as oil, Pluronic F68 as co-surfactant and Cremophore EL as surfactant using high speed stirring, followed by probe sonication. Nanoemulsion with average globule size of 100.9 nm and zeta potential of -35.9 ± 1.2 mV was able to penetrate well into the intestinal membrane as confirmed by the laser confocal scanning microscopy and ex vivo intestinal permeability study. Antimycotic study confirmed the efficacy of ITR nanoemulsion. Significantly higher values of pharmacokinetic parameters the formulation than the plain drug and marketed formulation indicated an increase in the bioavailability of ITR. The prepared nanoemulsion was stable at both, refrigerated and room temperature conditions. Nanoemulsion of ITR seems to be a promising formulation for enhancement of its oral bioavailability.


Asunto(s)
Antifúngicos/química , Emulsiones , Itraconazol/química , Nanomedicina/métodos , Administración Oral , Animales , Disponibilidad Biológica , Difusión , Excipientes , Glicéridos/química , Glicerol/análogos & derivados , Glicerol/química , Cinética , Masculino , Microscopía Confocal , Microscopía Electrónica de Transmisión , Tamaño de la Partícula , Permeabilidad , Poloxámero/química , Ratas , Ratas Sprague-Dawley , Tensoactivos/química , Temperatura
11.
J Microencapsul ; : 1-11, 2015 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-26242842

RESUMEN

Itraconazole (ITR), an antifungal agent has poor bioavailability due to low aqueous solubility. The present investigation aimed at development of ITR nanoemulsion to enhance its oral bioavailability. ITR nanoemulsion was prepared using Capmul MCM C8 as oil, Pluronic F68 as co-surfactant and Cremophore EL as surfactant using high speed stirring, followed by probe sonication. Nanoemulsion with average globule size of 100.9 nm and zeta potential of -35.9 ± 1.2 mV was able to penetrate well into the intestinal membrane as confirmed by the laser confocal scanning microscopy and ex vivo intestinal permeability study. Antimycotic study confirmed the efficacy of ITR nanoemulsion. Significantly higher values of pharmacokinetic parameters the formulation than the plain drug and marketed formulation indicated an increase in the bioavailability of ITR. The prepared nanoemulsion was stable at both, refrigerated and room temperature conditions. Nanoemulsion of ITR seems to be a promising formulation for enhancement of its oral bioavailability.

12.
AAPS PharmSciTech ; 16(6): 1434-44, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25991065

RESUMEN

The objective of the present work was to formulate tablet dosage form of itraconazole with enhanced bioavailability. Spherical crystal agglomerates (SCA) of itraconazole prepared by quasi emulsification solvent diffusion method using Soluplus and polyethylene glycol 4000 (PEG 4000) showed increased solubility (540 µg/ml) in 0.1 N hydrochloric acid as compared to pure drug (12 µg/ml). A Fourier transform infrared (FTIR) study indicated compatibility of drug with the excipients. The developed SCA were spherical with smooth surface having an average size of 412 µm. The significantly improved micromeritic properties compared to the plain drug suggested its suitability for direct compression. The antifungal activity of itraconazole was retained in the SCA form as evidenced from the results of the disc diffusion method. The optimized SCA formulation could be easily compressed into tablet with desirable characteristics of hardness (5 kg/cm(2)) and disintegration time (6.3 min). The in vitro dissolution studies showed significant difference in the dissolution profiles of pure drug (21%) and SCA formulation (85%) which was even greater than that of marketed preparation (75%). In vivo pharmacokinetic showed significant enhancement in C max and AUC0-t with relative bioavailability of 225%. The SCA formulation seems to be promising for enhancement of oral bioavailability of itraconazole.


Asunto(s)
Itraconazol/química , Comprimidos/química , Administración Oral , Antifúngicos/química , Disponibilidad Biológica , Rastreo Diferencial de Calorimetría/métodos , Química Farmacéutica/métodos , Cristalización/métodos , Excipientes/química , Dureza , Nanopartículas/química , Tamaño de la Partícula , Polietilenglicoles/química , Polivinilos/química , Solubilidad , Solventes/química
13.
AAPS PharmSciTech ; 15(4): 845-57, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24700295

RESUMEN

Cisplatin, first (platinum) compound to be evolved as an anticancer agent, has found its important place in cancer chemotherapy. However, the dose-dependent toxicities of cisplatin, namely nephrotoxicity, ototoxicity, peripheral neuropathy, and gastrointestinal toxicity hinder its widespread use. Liposomes can reduce the toxicity of cisplatin and provide a better therapeutic action, but the low lipid solubility of cisplatin hinders its high entrapment in such lipid carrier. In the present investigation, positively charged reactive aquated species of cisplatin were complexed with negatively charged caprylate ligands, resulting in enhanced interaction of cisplatin with lipid bilayer of liposomes and increase in its encapsulation in liposomal carrier. Prepared cisplatin liposomes were found to have a vesicular size of 107.9 ± 6.2 nm and zeta potential of -3.99 ± 3.45 mV. The optimized liposomal formulation had an encapsulation efficiency of 96.03 ± 1.24% with unprecedented drug loading (0.21 mg cisplatin / mg of lipids). The in vitro release studies exhibited a pH-dependent release of cisplatin from liposomes with highest release (67.55 ± 3.65%) at pH 5.5 indicating that a maximum release would occur inside cancer cells at endolysosomal pH. The prepared liposomes were found to be stable in the serum and showed a low hemolytic potential. In vitro cytotoxicity of cisplatin liposomes on A549 lung cancer cell line was comparable to that of cisplatin solution. The developed formulation also had a significantly higher median lethal dose (LD50) of 23.79 mg/kg than that of the cisplatin solution (12 mg/kg). A promising liposomal formulation of cisplatin has been proposed that can overcome the disadvantages associated with conventional cisplatin therapy and provide a higher safety profile.


Asunto(s)
Caprilatos/química , Cisplatino/química , Liposomas/química , Animales , Línea Celular Tumoral , Química Farmacéutica/métodos , Portadores de Fármacos/química , Femenino , Humanos , Concentración de Iones de Hidrógeno , Membrana Dobles de Lípidos/química , Ratones , Tamaño de la Partícula , Fosfolípidos/química , Solubilidad
14.
Pharmaceutics ; 15(1)2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36678853

RESUMEN

Febuxostat is a widely prescribed drug for the treatment of gout, which is a highly prevalent disease worldwide and is a major cause of disability in mankind. Febuxostat suffers from several limitations such as gastrointestinal disturbances and low oral bioavailability. Thus, to improve patient compliance and bioavailability, transdermal drug delivery systems of Febuxostat were developed for obtaining enhanced permeation. Cubosomes of Febuxostat were prepared using a bottom-up approach and loaded into a microneedle using a micromolding technique to achieve better permeation through the skin. Optimization of the process and formulation parameters were achieved using our design of experiments. The optimized cubosomes of Febuxostat were characterized for various parameters such as % entrapment efficiency, vesicle size, Polydispersity index, Transmission electron microscopy, in vitro drug release, Small angle X-ray scattering, etc. After loading it in the microneedle it was characterized for dissolution time, axial fracture force, scanning electron microscopy, in vitro drug release, pore closure kinetics, etc. It was also evaluated for various ex vivo characterizations such as in vitro cell viability, ex vivo permeation, ex vivo fluorescence microscopy and histopathology which indicates its safety and better permeation. In vivo pharmacokinetic studies proved enhanced bioavailability compared with the marketed formulation. Pharmacodynamic study indicated its effectiveness in a disease-induced rat model. The developed formulations were then subjected to the stability study, which proved its stability.

15.
Ther Deliv ; 14(2): 105-119, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-37125431

RESUMEN

Aim: Present research work aimed to explore intravaginal route for the drug delivery for treatment of endometrial cancer (EC). Material & methods: Carboplatin (CBP)-loaded ultradeformable vesicle (CBP-UDV) was prepared and characterized for in vitro quality attributes and evaluated for its efficacy in rabbits using ultrasound imaging after intravaginal administration. Results & conclusion: The results showed that the formulation capable of carrying and localizing drug in uterus for prolonged period assisted by first uterine pass effect. Ultrasound imaging of the EC-induced rabbit model before and after treatment with CBP-UDV showed considerable regression in the EC tumor mass. The findings serve as the basis of successful utilization of the intravaginal route for management of EC by designing the formulation which can improve patient compliance.


Asunto(s)
Sistemas de Liberación de Medicamentos , Neoplasias Endometriales , Humanos , Animales , Femenino , Conejos , Carboplatino , Sistemas de Liberación de Medicamentos/métodos , Administración Intravaginal , Neoplasias Endometriales/tratamiento farmacológico
16.
Ther Deliv ; 14(4): 269-280, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37340886

RESUMEN

Aim: The current research focused on formulation of spherical crystal agglomerates (SCA) of atazanavir sulphate for improving flow property and solubility. Materials & methods: SCA were formulated by quasi-emulsification solvent diffusion. Methanol, water and dichloromethane were employed as a good solvent, bad solvent and bridging liquid respectively. Results & conclusion: SCA with improved solubility and micromeritic properties were directly compressed into a tablet. The SCA tablets had higher dissolution rates compared with plain drug and marketed product. In vivo pharmacokinetic studies revealed higher Cmax and AUC0-t of the SCA than marketed product with relative bioavailability of 1.74. The formulation was stable for more than 3 months, with insignificant difference in % drug content and % drug dissolution.


Atazanavir sulphate is a drug used for treatment of AIDS in which the patients are infected with HIV. Presently, it is available as a capsule. The amount of the drug reaching the blood after oral delivery is less due to the poor solubility of the drug. Compared with capsules, tablets are more preferred dosage forms due to its ease of manufacturing and tamper proof nature. In the present research work, we have developed a tablet formulation of the drug, which has improved solubility. The higher solubility leads to greater absorption after oral delivery. Thus the formulation is beneficial to the patients as the dose can be reduced and the treatment can be made more economic.


Asunto(s)
Sulfato de Atazanavir , Disponibilidad Biológica , Solubilidad , Liberación de Fármacos , Solventes/química , Comprimidos/química , Administración Oral
17.
J Liposome Res ; 22(2): 139-47, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22149643

RESUMEN

Vincristine-sulfate-loaded liposomes were prepared with an aim to improve stability, reduce drug leakage during systemic circulation, and increase intracellular uptake. Liposomes were prepared by the thin-film hydration method, followed by coating with calcium phosphate, using the sequential addition approach. Prepared formulations were characterized for size, zeta potential, drug-entrapment efficiency, morphology by transmission electron microscopy (TEM), in vitro drug-release profile, and in vitro cell cytotoxicity study. Effect of formulation variables, such as drug:lipid ratio as well as nature and volume of hydration media, were found to affect drug entrapment, and the concentration of calcium chloride in coating was found to affect size and coating efficiency. Size, zeta potential, and TEM images confirmed that the liposomes were effectively coated with calcium phosphate. The calcium phosphate nanoshell exhibited pH-dependent drug release, showing significantly lower release at pH 7.4, compared to the release at pH 4.5, which is the pH of the tumor interstitium. The in vitro cytotoxicity study done on the lung cancer cell line indicated that coated liposomes are more cytotoxic than plain liposomes and drug solution, indicating their potential for intracellular drug delivery. The cell-uptake study done on the lung cancer cell line indicated that calcium-phosphate-coated liposomes show higher cell uptake than uncoated liposomes.


Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Fosfatos de Calcio/química , Sistemas de Liberación de Medicamentos , Liposomas/química , Nanocáscaras/química , Sulfatos/administración & dosificación , Vincristina/administración & dosificación , Vincristina/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración de Iones de Hidrógeno , Liposomas/síntesis química , Liposomas/farmacología , Tamaño de la Partícula , Relación Estructura-Actividad , Sulfatos/química , Sulfatos/farmacología , Propiedades de Superficie , Distribución Tisular
18.
AAPS PharmSciTech ; 13(4): 1502-10, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23104306

RESUMEN

The aim was to develop niosomal gel as a transdermal nanocarrier for improved systemic availability of lopinavir. Niosomes were prepared using thin-film hydration method and optimized for molar quantities of Span 40 and cholesterol to impart desirable characteristics. Comparative evaluation with ethosomes was performed using ex vivo skin permeation, fluorescence microscopy, and histopathology studies. Clinical utility via transdermal route was acknowledged using in vivo bioavailability study in male Wistar rats. The niosomal formulation containing lopinavir, Span 40, and cholesterol in a molar ratio of 1:0.9:0.6 possessed optimally high percentage of drug entrapment with minimum mean vesicular diameter. Ex vivo skin permeation studies of lopinavir as well as fluorescent probe coumarin revealed a better deposition of ethosomal carriers but a better release with niosomal carriers. Histopathological studies indicated the better safety profile of niosomes over ethosomes. In vivo bioavailability study in male Wistar rats showed a significantly higher extent of absorption (AUC(0→∞), 72.87 h × µg/ml) of lopinavir via transdermally applied niosomal gel as compared with its oral suspension. Taken together, these findings suggested that niosomal gel holds a great potential of being utilized as novel, nanosized drug delivery vehicle for transdermal lopinavir delivery.


Asunto(s)
Geles/química , Liposomas/química , Lopinavir/administración & dosificación , Lopinavir/química , Administración Cutánea , Administración Oral , Animales , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/química , Disponibilidad Biológica , Química Farmacéutica/métodos , Colesterol/química , Cumarinas/administración & dosificación , Cumarinas/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Geles/administración & dosificación , Liposomas/administración & dosificación , Masculino , Tamaño de la Partícula , Permeabilidad , Ratas , Ratas Wistar , Piel/metabolismo , Absorción Cutánea , Suspensiones/administración & dosificación , Suspensiones/química
19.
Ther Deliv ; 13(7): 371-381, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-36416617

RESUMEN

One of the principal impediments for the treatment of neurological conditions is the lack of ability of most of the medicinal agents to evade the blood-brain barrier. Among all the novel approaches to bypass the blood-brain barrier, nose to brain transport is the most patient compliant, non-invasive and effective approach. It directly transports drugs to the CNS via the trigeminal and olfactory nerves present in the nasal cavity. This review article focuses on anatomy and physiology of nasal cavity, potential of intranasal drug delivery, mechanisms of drug transport to brain, its advantages and limitations, novel intranasal formulations, marketed products, factors affecting nose to brain transport, formulation consideration of intranasal products and the future perspectives of CNS targeting via intranasal drug administration.


Asunto(s)
Barrera Hematoencefálica , Nariz , Humanos , Administración Intranasal , Encéfalo , Sistemas de Liberación de Medicamentos
20.
Int J Pharm ; 624: 122045, 2022 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-35878872

RESUMEN

Omiganan is a novel 12 amino acid synthetic cationic peptide from the cathelicidin family. Omiganan possesses antimicrobial action against a wide range of microbes, including gram-positive and gram-negative bacteria and fungi. Omiganan mainly acts by depolarizing the cytoplasmic membrane, resulting in cellular disruption and death. Apart from its antimicrobial effect, Omiganan also has anti-inflammatory activity. The present investigation aimed to evaluate and compare the efficacy of Omiganan liposomal gel with conventional formulations (Omiganan gel and lotion) in atopic dermatitis (AD) and psoriasis mice animal models. Liposomes encapsulating Omiganan were prepared using the reverse-phase evaporation technique and incorporated into Carbopol 934P gel. The optimized Omiganan liposomes were then characterized for various physicochemical parameters such as vesicle size, shape and surface morphology, zeta-potential, rheological parameters, in-vitro drug release, ex-vivo skin permeation/deposition, in-vitro antimicrobial activity, proteolytic stability, and cellular toxicity and uptake studies. Liposomes exhibited 72 % encapsulation with 7.8 % loading efficacy, a vesicle size, and zeta potential of 120 nm and - 17.2 mv, respectively. Moreover, Omiganan liposomal gel demonstrated controlled release and a better permeation profile than conventional formulations. A substantial reduction in levels of pro-inflammatory cytokines and improvement in AD and psoriatic lesions were achieved by Omiganan liposomal gel compared to Omiganan gel and lotion-based formulations. The present study confirms that Omiganan liposomal formulation can be an effective, safe, and novel alternative treatment approach in atopic dermatitis and psoriasis.


Asunto(s)
Dermatitis Atópica , Psoriasis , Animales , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos , Péptidos Antimicrobianos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/metabolismo , Modelos Animales de Enfermedad , Bacterias Gramnegativas , Bacterias Grampositivas , Liposomas/química , Ratones , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Piel/metabolismo
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