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Lipid and/or polymer-based drug conjugates can potentially minimize side effects by increasing drug accumulation at target sites and thus augment patient compliance. Formulation factors can present a potent influence on the characteristics of the obtained systems. The selection of an appropriate solvent with satisfactory rheological properties, miscibility, and biocompatibility is essential to optimize drug release. This work presents a computational study of the effect of the basic formulation factors on the characteristics of the obtained in situ-forming particulates (IFPs) encapsulating a model drug using a 21.31 full factorial experimental design. The emulsion method was employed for the preparation of lipid and/or polymer-based IFPs. The IFP release profiles and parameters were computed. Additionally, a desirability study was carried out to choose the optimum formulation for further morphological examination, rheological study, and PBPK physiological modeling. Results revealed that the type of particulate forming agent (lipid/polymer) and the incorporation of structure additives like Brij 52 and Eudragit RL can effectively augment the release profile as well as the burst of the drug. The optimized formulation exhibited a pseudoplastic rheological behavior and yielded uniformly spherical-shaped dense particulates with a PS of 573.92 ± 23.5 nm upon injection. Physiological modeling simulation revealed the pioneer pharmacokinetic properties of the optimized formulation compared to the observed data. These results assure the importance of controlling the formulation factors during drug development, the potentiality of the optimized IFPs for the intramuscular delivery of piroxicam, and the reliability of PBPK physiological modeling in predicting the biological performance of new formulations with effective cost management.
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Intra-articular (IA) injection is grasping much interest due to the poor drug bioavailability at the targeted site of action which minimizes the effect of the orally administered moiety. Based on the integral role of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of Rheumatoid Arthritis (RA), much effort is exerted to develop novel localized drug delivery systems to increase their bioavailability and minimize their side effects. Artificial intelligence (AI) is acquiring an increasing role in the design of experiments being an effective tool for saving both time and resources. Hence, the aim of this work was to develop, characterize and optimize targeted in-situ forming nano particles (ISNs) for IA delivery of piroxicam using Design® Expert as an AI-based application where a 33 full factorial experimental design was adopted. Morphological investigation, injectability, rheological studies, Fourier Transform Infrared Radiation (FTIR) as well as biological, histopathological, and biochemical examinations were performed to evaluate the optimized-ISNs. The optimized formulation, exhibiting a nano-sized particle size with a dense core, showed significant improvement in the histopathological findings compared to both the oral solution and the placebo. Additionally, the once-a-week IA administration of the optimized-ISNs proved a significant reduction in the protein expression of both STAT-3 and RANKL and the levels of anti-CCP and MCP-1 by almost 54 and 73%, respectively, coupled with a marked decline in the content of IL-17, MMP-3, NF-κB and TNF-α as compared to the positive control. In conclusion, the use of ISNs for intra-articular injection has demonstrated their effectiveness in piroxicam delivery for RA treatment.
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Artritis Reumatoide , Nanopartículas , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Inteligencia Artificial , Sistemas de Liberación de Medicamentos , Humanos , Inyecciones Intraarticulares , Nanopartículas/química , PiroxicamRESUMEN
A promising approach has been emerging to enhance dissolution of hydrophobicdrugsby encapsulation in mesoporous silica materials. Olanzapine is a practically insoluble antipsychotic drug which is subjected to excessive first pass effect and shows inadequate oral bioavailability. Therefore, mesoporous silica was used to improve bioavailability of olanzapine incorporated in nano-structured lipid carriers (NLCs). These systems were characterized for their particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE) and differential scanning calorimetry (DSC) as well asits release profile. The optimized mesoporous NLC system displayed nano-spherical particles (120.56 nm), possessed high entrapment efficiency (88.46%) and the highest percentage of drug released after six hours (75.13%). The biological performance of the optimized system was assessed in comparison with the drug suspension in healthy albino rabbits. The optimized system showed significantly (P < 0.05) prolonged MRT (8.47 h), higher Cmax (22.12± 0.40 ng/ml) and Tmax (2.0 h) values compared to drug suspension. Physiologically based pharmacokinetic (PBPK) model was simulated and verified. All the predicted results were within 0.6 and 1-fold of the reported data. To set a conclusion, in vitro results as well as in vivo pharmacokinetic study and PBPK data showed an enhancement in bioavailability of the optimized NLCs system over the plain drug suspension. These results proved the potentiality of incorporating olanzapine in mesoporous NLC for a significant improvement in oral bioavailability of olanzapine.
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Portadores de Fármacos , Nanoestructuras , Administración Oral , Animales , Lípidos , Olanzapina , Tamaño de la Partícula , ConejosRESUMEN
AIM: The aim of the current work was to develop vardenafil hydrochloride (VRD)-loaded ethosome-derived invasomes as a possible transdermal system which could be used for patients suffering from pulmonary arterial hypertension. METHODS: VRD-loaded ethosomes were developed at three concentrations of phosphatidylcholine (5, 10 and 15 mg/mL) and three percentages of ethanol (20%, 30% and 40%, v/v). The best achieved VRD-loaded ethosomes (ETH9) were optimized to invasomes via incorporation of terpenes (limonene, cineole and a 1:1 mixture) at three concentrations (0.5%, 1% and 2%, v/v). All systems were evaluated for vesicle size, zeta potential, drug entrapment efficiency (EE%), cumulative drug permeated percentages after 0.5hrs (Q0.5h) and 12hrs (Q12h) and steady-state flux (Jss). The optimized system (ETH9-INV8) was further characterized for morphology, histopathology and confocal laser scanning microscopy (CLSM). Physiologically based pharmacokinetic (PBPK) modeling was employed to estimate VRD pharmacokinetic parameters from the optimized transdermal system and an oral aqueous drug dispersion, in adults and geriatrics. RESULTS: The optimized invasomal system (ETH9-INV8) was characterized with spherical vesicles (159.9 nm) possessing negative zeta potential (-20.3 mV), promising EE% (81.3%), low Q0.5h (25.4%), high Q12h (85.3%) and the largest steady-state flux (6.4 µg.cm-2h-1). Following a leave-on period of 12hrs in rats, it showed minor histopathologic changes. CLSM studies proved its ability to deeply permeate rat skin. Lower Cmax values, delayed Tmax estimates and greater AUC0-24h folds in adults and geriatrics (≈ 2.18 and 1.69, respectively) were estimated following the transdermal application of ETH9-INV8 system. CONCLUSION: ETH9-INV8 is a promising transdermal system for VRD.
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Sistemas de Liberación de Medicamentos , Etanol/química , Geriatría , Modelos Biológicos , Diclorhidrato de Vardenafil/administración & dosificación , Diclorhidrato de Vardenafil/farmacocinética , Administración Cutánea , Animales , Liposomas , Masculino , Microscopía Confocal , Tamaño de la Partícula , Permeabilidad , Ratas Wistar , Absorción Cutánea , Electricidad EstáticaRESUMEN
This review addressed erectile dysfunction, regarding pathophysiology and therapeutic strategies. The line of treatment includes phosphodiesterase type-5 inhibitors and other types of therapy like topical and stem-cell transplant. Scientific literature was assessed to investigate the impact of nanotechnology on erectile dysfunction therapy. Various nanotechnology approaches were applied, like vesicular systems, lipid-based carriers, nanocrystals, dendrimers, liquid crystalline systems and nanoemulsions. Smart nano-systems can alter the landscape of the modern pharmaceutical industry by re- investigation of pharmaceutically suboptimal but biologically active entities for treatment of erectile dysfunction which were previously considered undeveloped.
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Disfunción Eréctil/terapia , Nanomedicina/métodos , Dopaminérgicos/uso terapéutico , Terapia Genética/métodos , Humanos , Masculino , Nanopartículas/uso terapéutico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Receptores de Melanocortina/agonistasRESUMEN
Pulmonary delivery of vasodilators is a promising alternative for the intravenous and oral treatment of pulmonary arterial hypertension (PAH). The aim of this study was to design and evaluate hydrogel microparticles as a carrier for sustained pulmonary delivery of sildenafil citrate. Spray dried hydrogel microparticles containing biodegradable sodium carboxymethyl cellulose, sodium alginate, and sodium hyaluronate polymers at variable concentrations were prepared. A design of experiment using the "Extreme Vertices Mixture" design was executed. The design was used to study the influence of polymer concentration and their interactions on the physicochemical properties of the formulations in terms of particle size, particle size distribution, product yield, entrapment efficiency, and in-vitro drug release. Selected formulations were also evaluated for swelling, biodegradation, moisture content, in-vitro aerodynamic performance, and cytotoxicity. In addition, a lung deposition and pharmacokinetic study was conducted in rats to study drug accumulation in lungs and blood after intratracheal administration of the spray dried inhalable hydrogel microparticles in comparison to orally administered Viagra®. The results demonstrated that formulated microparticles had a mean geometric particle size between 2 and 5⯵m, entrapment efficiency of >80%, and yield ranging between 47 and 66% w/w. The in-vitro drug release profiles showed a sustained drug release of sildenafil citrate for over 24â¯h. The statistical design showed a significant influence of the microparticulate composition on the physicochemical properties. Furthermore, selected formulations were evaluated for their aerodynamic properties. The aerodynamic properties included fine particle fraction ranging between 24 and 30%, dose recovery percent of 68-8 5%, and average mass median aerodynamic diameter of 4.6-4.8⯵m. The in-vivo pharmacokinetic study showed that inhaled spray dried hydrogel microparticles (M6) formulation had significantly higher lung/blood Cmax, AUC, extended half-life, and mean residence time in comparison to orally administered sildenafil citrate of the same dose. In conclusion, the formulated drug-loaded spray dried hydrogel microparticles showed promising in-vitro and in-vivo results for the pulmonary delivery of sildenafil citrate. The spray dried hydrogel microparticles formulation can be considered as a potential alternative of oral sildenafil citrate for treatment of PAH.
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Portadores de Fármacos/química , Hipertensión Pulmonar Primaria Familiar/tratamiento farmacológico , Polvos/administración & dosificación , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Citrato de Sildenafil/administración & dosificación , Administración por Inhalación , Administración Oral , Alginatos/química , Animales , Carboximetilcelulosa de Sodio/química , Preparaciones de Acción Retardada/química , Composición de Medicamentos , Liberación de Fármacos , Inhaladores de Polvo Seco , Humanos , Ácido Hialurónico/química , Hidrogeles/química , Pulmón/metabolismo , Masculino , Ratones , Microesferas , Tamaño de la Partícula , Polvos/química , Polvos/uso terapéutico , Células RAW 264.7 , Ratas , Citrato de Sildenafil/química , Citrato de Sildenafil/uso terapéutico , Propiedades de Superficie , Distribución TisularRESUMEN
Ondansetron hydrochloride (OND) is commonly used for management of postoperative and chemotherapeutic-induced nausea and vomiting. It suffers from low bioavailability (60%) and rapid elimination (t1/2; 3-4 h). The current work aimed to develop OND-loaded bilosomes as a promising transdermal delivery system capable of surmount drug limitations. The variables influencing the development of OND-loaded bilosomes and niosomes (18 systems) via the thin film hydration technique were investigated, including surfactant type (Span®60 or Span®80), surfactant/cholesterol molar ratio (7:0, 7:1, or 7:3), and sodium deoxycholate (SDC) concentration (0, 2.5, or 5%, w/v). The systems were characterized for particle size, polydispersity index, zeta potential, drug entrapment efficiency (EE%), and in vitro permeation. Based on factorial analysis (32·21) and calculations of desirability values, six systems were further subjected to ex vivo permeation through excised rat skin, differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and transmission electron microscopy. Histopathological and in vivo permeation studies in rats were conducted on the best achieved system (B6) in comparison to drug solution. Higher desirability values were achieved with Span® 60-based bilosomes, surfactant/cholesterol molar ratio of 7:1, and SDC concentration of 2.5% w/v with respect to small vesicle size, polydispersity index and high zeta potential, EE%, and cumulative drug permeation. OND was dispersed in amorphous state as revealed from DSC and PXRD studies. No marked effect was observed in rat skin following application of B6 system while higher ex vivo and in vivo cumulative permeation profiles were revealed. Bilosomal systems were considered as safe and efficient carriers for the transdermal delivery for OND.
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Antieméticos/administración & dosificación , Antieméticos/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Ondansetrón/administración & dosificación , Ondansetrón/metabolismo , Absorción Cutánea/efectos de los fármacos , Administración Cutánea , Animales , Animales Recién Nacidos , Disponibilidad Biológica , Rastreo Diferencial de Calorimetría , Liposomas , Masculino , Microscopía Electrónica de Transmisión , Tamaño de la Partícula , Ratas , Piel/efectos de los fármacos , Piel/metabolismo , Absorción Cutánea/fisiología , Tensoactivos/química , Difracción de Rayos XRESUMEN
Management of epilepsy requires brain delivery therapy, therefore, this study was aimed to prepare lamotrigine loaded poly-É-(d,l-lactide-co-caprolactone) (PLCL) nanoparticles using spontaneous emulsification solvent diffusion method. Nanoparticles for brain delivery required to have a particle size <200â¯nm, polydispesity index <0.2 and a sustained drug release properties. For such aim different factors were considered in preparing the nanoparticles as PLCL monomers' ratio, type of organic solvent used to prepare the nanoparticles, amount of PLCL and Pluronic®F127 in the nanoparticles. Prepared nanoparticles were characterized for their shape, particle size, polydispersity index, zeta potential, encapsulation efficiency, drug loading capacity, process yield and in-vitro drug release pattern. The in-vivo investigation for brain delivery of selected nanoparticles delivered by intravenous route was investigated in rats and compared to that for oral tablet. The obtained nanoparticles were spherical in shape. The amount of surfactant and PLCL affected the properties of the obtained nanoparticles. Using a mixture of organic solvent in preparing the nanoparticles improved its properties. The nanoparticles prepared using PLCL with monomers' ratio of 25:75, had particle size value of 125â¯nm, polydispersity index value of 0.184, zeta potential value of -39â¯mV and encapsulation efficiency value of 99%, was selected to study their efficacy to deliver the drug to the brain. The tested nanoparticles showed higher values of Tmax, Cmax, AUC, and MRT in homogenized rat brain, compared to oral lamotrigine tablet, while the bioavailability of the oral tablet was higher in rat plasma compared to that for the nanoparticles. This reflects that brain was the main distribution site for tested nanoparticles, and plasma was the main distribution site for oral tablets. This confirms the goal of the selected formulation as brain delivery nanoparticles.
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Encéfalo/efectos de los fármacos , Caproatos/química , Dioxanos/química , Lactonas/química , Nanopartículas/química , Triazinas/química , Animales , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos/efectos de los fármacos , Lamotrigina , Tamaño de la Partícula , Ratas , Ratas Wistar , Comprimidos/químicaRESUMEN
Non-ionic surfactant (NIS) based in situ forming vesicles (ISVs) present an affordable alternative to the traditional systems for the parenteral control of drug release. In this work, NIS based ISVs encapsulating tenoxicam were prepared using the emulsion method. Tenoxicam-loaded ISVs were prepared using a 22.31 full factorial experimental design, where three factors were evaluated as independent variables; type of NIS (A), molar ratio of NIS to Tween®80 (B), and phase ratio of the internal ethyl acetate to the external Captex® oil phase (C). Percentage drug released after 1 h, particle size of the obtained vesicles and mean dissolution time were chosen as the dependent variables. Selected formulation was subjected to morphological investigation, injectability, viscosity measurements, and solid state characterization. Optimum formulation showed spherical nano-vesicles in the size of 379.08 nm with an initial drug release of 37.32% in the first hour followed by a sustained drug release pattern for 6 days. DSC analysis of the optimized formulation confirmed the presence of the drug in an amorphous form with the nano-vesicles. Biological evaluation of the selected formulation was performed on New Zealand rabbits by IM injection. The prepared ISVs exhibited a 45- and 28-fold larger AUC and MRT values, respectively, compared to those of the drug suspension. The obtained findings boost the use of ISVs for the treatment of many chronic inflammatory conditions.
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Portadores de Fármacos/química , Tensoactivos/química , Animales , Preparaciones de Acción Retardada , Liberación de Fármacos , Emulsiones , Masculino , Tamaño de la Partícula , Piroxicam/administración & dosificación , Piroxicam/análogos & derivados , Polisorbatos , ConejosRESUMEN
BACKGROUND: Fenoprofen calcium dehydrate (FCD) is counted as a non-steroidal, anti-inflammatory, anti-arthritic drug. FCD is slightly water soluble. It is indicated for mild pain relief, where the suggested dosage is 200 mg orally every 4 to 6 h. AIM: Reduce dissolution efficiency, reach an extended therapeutic effect and reduce the frequency of the drug side effects. METHOD: Combination of the co-evaporated drug:triacetyl-ß-cyclodextrin complex prepared in a ratio of 1:3 and either of two polymers-hydroxylpropylmethyl cellulose (HPMC) or ethyl cellulose (EC)-in the same formulation. Invitro dissolution studies were carried in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids, by using the USP dissolution tester (rotating paddle apparatus). The FCD in vitro release from EC/drug complex was markedly retarded. Interaction between fenoprofen, TA-ß-CD, EC, HPMC in the solid state were confirmed by FT-IR, DSC, XRD and SEM. In vivo studies assessed the anti-inflammatory and analgesic activities and the results were compared with the market product Nalfosab® Capsules. RESULTS: Remarkable inhibition of inflammation and nociception after 24 h was attained for EC/drug complex. CONCLUSIONS: EC/drug complex has a sustained effect due to high remaining amount after elapsing with remarkable inhibition of inflammation.
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CONTEXT: Topical treatment of skin disease needs to be strategic to ensure high drug concentration in the skin with minimum systemic absorption. OBJECTIVE: The aim of this study was to produce semisolid nanostructured lipid carrier (NLC) formulations, for topical delivery of the corticosteroid drug, diflucortolone valerate (DFV), with minimum systemic absorption. METHOD: NLC formulations were developed using a high shear homogenization combined with sonication, using Precirol® ATO5 or Tristearin® as the solid lipid, Capryol™ or isopropyl myristate as the liquid lipid and Poloxamer® 407 as surfactant. The present study addresses the influence of different formulations composition as solid lipid, liquid lipid types and concentrations on the physicochemical properties and drug release profile from NLCs. RESULTS AND DISCUSSION: DFV-loaded NLC formulations possessed average particle size ranging from 160.40 nm to 743.7 nm with narrow polydispersity index. The encapsulation efficiency was improved by adding the lipid-based surfactants (Labrasol® and Labrafil® M1944CS) to reach 68%. The drug release from the investigated NLC formulations showed a prolonged release up to 12 h. The dermatopharmacokinetic study revealed an improvement in drug deposition in the skin with the optimized DFV-loaded NLC formulation, in contrast to a commercial formulation. CONCLUSION: NLC provides a promising nanocarrier system that work as reservoir for targeting topical delivery of DFV.
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Diflucortolona/análogos & derivados , Sistemas de Liberación de Medicamentos , Lípidos/química , Nanoestructuras/química , Diflucortolona/administración & dosificación , Diflucortolona/química , Diflucortolona/farmacocinética , Portadores de Fármacos/química , Composición de Medicamentos , Humanos , Tamaño de la Partícula , Piel/efectos de los fármacos , Propiedades de Superficie , Distribución TisularRESUMEN
Fluticasone propionate is a synthetic corticosteroid drug distinguished by its potent anti-inflammatory action with low systemic side effects in comparison to other corticosteroids making it a potential drug for local buccal delivery. The aim of the present study was to design mucoadhesive buccal film containing fluticasone that is aesthetically acceptable and could maintain local drug release for a sustained period to manage the sign and symptoms of severe erosive mouth lesions. Solvent casting technique was used in film preparation. Different polymeric blends were used either alone or in combination with mucoadhesive polymers, sodium carboxymethyl cellulose (SCMC), or Carbopol 971P at different concentrations. The physicochemical properties, in vitro mucoadhesion time as well as the drug release properties for all prepared formulations were determined. Selected formulations with adequate properties were further examined by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) and subjected to in vivo evaluation. Films containing hydroxypropyl methylcellulose (HPMC)/ethyl cellulose (EC) showed acceptable physicochemical properties, homogenous drug distribution, convenient mucoadhesion time, moderate swelling as well as sustained drug release up to 12 h. The biological performance of these formulations was assessed on healthy human volunteers and compared with a prepared mouthwash which showed enhanced pharmacokinetic parameters for the selected films in comparison to the mouthwash. The results revealed that the optimized formulation containing HPMC/EC and 10% SCMC could successfully achieve sustained drug release for 10 h which is considered promising for local treatment of severe mouth lesions.
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Adhesivos/administración & dosificación , Adhesivos/química , Fluticasona/administración & dosificación , Fluticasona/química , Mucosa Bucal/metabolismo , Adhesividad/efectos de los fármacos , Administración Bucal , Adulto , Carboximetilcelulosa de Sodio/química , Celulosa/análogos & derivados , Celulosa/química , Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos/métodos , Femenino , Humanos , Derivados de la Hipromelosa/química , Masculino , Persona de Mediana Edad , Polímeros/química , Difracción de Rayos X/métodosRESUMEN
This study is focused on the design of gastro-retentive drug delivery system composed of hollow microspheres (microballoons) for the sustained delivery of cinnarizine (CIN). The microballoons (MBs) were prepared by the emulsion solvent diffusion method using cellulose acetate butyrate (CAB) as the hosting polymer and absolute ethanol (ETH) and dichloromethane (DCM) as solvents. A 3(3) full factorial experimental design was adopted to study the effect of different variables and to find an optimum formula with desired properties. Prepared microballoons showed high drug loading capacities and controlled release behaviour. The optimum formulation was chosen on the basis of achieving maximum values for both drug loading capacity and release efficiency as well as having suitable size. The optimized MB (MB-F21) was composed of 200 mg CIN and 400 mg CAB with a DCM/ETH ratio of 2:1. Scanning electron microscopy for the optimum formulation showed a spherical outline with internal porous structure. An in vivo study using human volunteers was performed by determination of CIN concentration in the plasma using the liquid chromatography-mass spectrometry (LC-MS) method. Results proved the superiority of the designed formulation over the market product Stuval® tablets in bioavailability parameters comprising T max as well as area under the plasma CIN concentration-time curve (AUC0-24 h) and AUC0-∞ values. Also, the significantly greater value of mean residence time (MRT) in case of MB-F21 indicates its higher gastric residence time and proves the advantages of micro-multiparticulate dosage forms over conventional one.
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Cinarizina/farmacocinética , Microesferas , Adulto , Disponibilidad Biológica , Celulosa/análogos & derivados , Celulosa/química , Cinarizina/sangre , Cinarizina/química , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Etanol/química , Humanos , Masculino , Cloruro de Metileno/química , Microscopía Electrónica de RastreoRESUMEN
The aim of this study was to formulate a microparticulate delivery system to deliver cinnarizine (CIN) directly to its site of absorption to overcome its low oral bioavailability. Enteric microparticles were prepared by varying ratios of pH-sensitive polymers (Eudragit L100 and Eudragit S100). A full 3(3) factorial experimental design was adopted to evaluate the effect of variables (CIN concentration as well as Eudragit's concentration) on the tested parameters, namely, particle size (p.s.), drug entrapment efficiency (E.E.), and release efficiency (R.E.). Optimization was done using Design Expert® software to maximize E.E. and R.E. and minimize p.s. The optimized formula was characterized using scanning electron microscopy, differential scanning calorimetry, and X-ray diffractometry. In vivo studies conducted on human volunteers using LC-MS analysis revealed improved bioavailability of CIN-loaded enteric microparticles compared to the market product as detected from calculated pharmacokinetic parameters. This study reveals the usefulness of site-specific delivery of CIN.
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Cinarizina/administración & dosificación , Cinarizina/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Microesferas , Administración Oral , Adulto , Disponibilidad Biológica , Cinarizina/sangre , Cinarizina/química , Liberación de Fármacos , Humanos , Concentración de Iones de Hidrógeno , Masculino , Tamaño de la Partícula , Ácidos Polimetacrílicos/químicaRESUMEN
Antiadherents are used to decrease tackiness of a polymer coating during both processing and subsequent storage. Despite being a common excipient in coating formulae, antiadherents may affect mechanical properties of the coating film as well as drug release from film-coated tablets, but how could addition of antiadherents affect these properties and to what extent and is there a relation between the physical characteristics of the tablet coat and the drug release mechanisms? The aim of this study was to evaluate physical characteristics of films containing different amounts of the antiadherents talc, glyceryl monostearate, and PlasACRYL(TM) T20. Eudragit RL30D and Eudragit RS30D as sustained release polymers and Eudragit FS30D as a delayed release material were used. Polymer films were characterized by tensile testing, differential scanning calorimetry (DSC), microscopic examination, and water content as calculated from loss on drying. The effect of antiadherents on in vitro drug release for the model acetylsalicylic acid tablets coated with Eudragit FS30D was also determined. Increasing talc concentration was found to decrease the ability of the polymer films to resist mechanical stress. In contrast, glyceryl monostearate (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher than 25% caused negative effects, which make 25% concentration recommended to be used with acrylic polymers. All antiadherents delayed the drug release at all coating levels; hence, different tailoring of drug release may be achieved by adjusting antiadherent concentration with coating level.
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Resinas Acrílicas/farmacocinética , Liberación de Fármacos , Polímeros/farmacocinética , Ácidos Polimetacrílicos/farmacocinética , Resinas Acrílicas/química , Polímeros/química , Ácidos Polimetacrílicos/químicaRESUMEN
Rice bran oil and its bioactive constituents have been reported to possess different health benefit effects. Rice bran oil-containing pharmaceutical and cosmeceutical formulae are dispensed and characterized to elucidate the impact of their properties on clinical applications. Liquisolid and semisolid formulations employing rice bran oil were dispensed and characterized. Semisolid formulae were characterized for organoleptic properties, rheological behavior, and physical stability, at zero time and after three months storage, at 30 degrees C and 40 degrees C. Patch test of transdermal emollient creams and sunscreen was conducted in addition to evaluation of sensory attributes of emollient cream and sunscreen. Liquisolid formulations revealed flow and bulk density figures close to those reported as optimum acceptable values for powders. Semisolid formulations revealed adequate properties after three months of storage compared with zero time. Patch test showed safety of transdermal and emollient creams and sunscreen. Sensory evaluation of cosmetics showed satisfactory results. Results indicate the high potential of the formulated rice bran oil products regarding physical properties, stability, and acceptance by consumers. The formulae are simple to dispense, cost effective, and highly accepted by consumers. These facts pave the way for future clinical trials involving these products.
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Grasas Insaturadas en la Dieta , Aceites de Plantas/química , Química Farmacéutica , Estabilidad de Medicamentos , Aceite de Salvado de ArrozRESUMEN
This study is an extrapolation of our previous one (part I) concerned with the formulation and physicochemical evaluation of a novel, simple, monolayer, easy-to-use, cost-effective, and aesthetically acceptable bioadhesive transdermal patch for tramadol hydrochloride. The current work is focused on bioadhesion, skin tolerability, and pharmacodynamic evaluation. Using naked rat skin, chitosan-Eudragit NE30D (1:1) film attained best bioadhesive properties. During in vivo studies, it also showed a significantly extended analgesic effect compared to both oral formula and chitosan single polymeric film using the hot plate test method. All the polymeric films were skin tolerable for the intended period of application according to the Draize test. The success of our approach can proudly, positively contribute into the world of pain management and arguably push transdermal delivery to realize its great promise.
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Analgésicos Opioides/administración & dosificación , Tramadol/administración & dosificación , Adhesividad , Administración Cutánea , Analgésicos Opioides/química , Analgésicos Opioides/farmacología , Animales , Química Farmacéutica , Quitosano , Preparaciones de Acción Retardada , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Irritantes/toxicidad , Masculino , Ratones , Dimensión del Dolor/efectos de los fármacos , Polímeros , Ácidos Polimetacrílicos , Ratas , Ratas Wistar , Piel/química , Piel/citología , Tramadol/química , Tramadol/farmacologíaRESUMEN
Dilutable nanoemulsions are potent drug delivery vehicles for ophthalmic use due to their numerous advantages as sustained effect and high ability of drug penetration into the deeper layers of the ocular structure and the aqueous humor. The aim of this article was to formulate the antiglaucoma drug dorzolamide hydrochloride as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Thirty-six systems consisting of different oils, surfactants, and cosurfactants were prepared and their pseudoternary-phase diagrams were constructed by water titration method. Seventeen dorzolamide hydrochloride nanoemulsions were prepared and evaluated for their physicochemical and drug release properties. These nanoemulsions showed acceptable physicochemical properties and exhibited slow drug release. Draize rabbit eye irritation test and histological examination were carried out for those preparations exhibiting superior properties and revealed that they were nonirritant. Biological evaluation of dorzolamide hydrochloride nanoemulsions on normotensive albino rabbits indicated that these products had higher therapeutic efficacy, faster onset of action, and prolonged effect relative to either drug solution or the market product. Formulation of dorzolamide hydrochloride in a nanoemulsion form offers, thus, a more intensive treatment of glaucoma, a decrease in the number of applications per day, and a better patient compliance compared to conventional eye drops.