RESUMEN
Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.
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Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/fisiopatología , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Animales , Antivirales/administración & dosificación , Antivirales/inmunología , Camelus/virología , Quirópteros/virología , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/transmisión , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Arabia Saudita/epidemiología , Zoonosis Virales/epidemiología , Zoonosis Virales/inmunología , Zoonosis Virales/transmisiónRESUMEN
This work was aimed to formulate topical Apremilast (APM)-loaded nanostructured lipid carriers (NLCs) for the management of psoriasis. NLCs were prepared by a cold homogenization technique using Compritol 888ATO, oleic acid, Tween 80 and Span 20, and Transcutol P as a solid lipid, liquid lipid, surfactant mixture, and penetration enhancer, respectively. Carbopol 940 was used to convert NLC dispersion into NLC-based hydrogel to improve its viscosity for topical administration. The optimized formulation was characterized for size, polydispersity index (PDI), zeta potential (ZP), percentage of entrapment efficiency (%EE), and surface morphology. Furthermore, viscosity, spreadability, stability, in vitro drug diffusion, ex vivo skin permeation, and skin deposition studies were carried out. APM-loaded NLCs showed a narrow PDI (0.339) with a particle size of 758 nm, a %EE of 85.5%, and a ZP of -33.3 mV. Scanning electron microscopy confirmed spherical shape of NLCs. in vitro drug diffusion and ex vivo skin permeation results showed low drug diffusion, sustained drug release, and 60.1% skin deposition. The present study confirms the potential of the nanostructured lipid form of poorly water-soluble drugs for topical application and increased drug deposition in the skin.
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Portadores de Fármacos , Nanopartículas , Liberación de Fármacos , Humanos , Lípidos , Talidomida/análogos & derivadosRESUMEN
BACKGROUND: Tinidazole (TNZ) is an anti-parasite drug used in the treatment of a variety of amebic and parasitic infections. It has low solubility in aqueous media and is categorized under Class II of the Biopharmaceutical Classification System. OBJECTIVES: The aim of this research was to study the potential for enhancing the solubility of TNZ using carboxylic acid co-crystals. MATERIAL AND METHODS: The solubility of TNZ was determined individually using 6 carboxylic acids for forming co-crystals at a 1:1 stoichiometric ratio. Three carboxylic acids - namely tartaric acid (TA), oxalic acid (OA) and glutaric acid (GA) - resulted in the formation of co-crystals with enhanced solubility. An equilibrium solubility study of TNZ co-crystals at 1:1.5 and 1:2 stoichiometric ratios was also carried out. The co-crystals which developed were evaluated using X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) to study the drug-co-crystal former interactions. RESULTS: The solubility of TNZ in distilled water was found to be 0.014 mg/mL. The highest enhancement ratio was obtained with TNZ and TA at a ratio of 1:1. Differential scanning calorimetry thermograms suggested that the drug and carboxylic acids had undergone interactions such as hydrogen bonding. The XRD and DSC results confirmed the formation of co-crystals. CONCLUSIONS: It was concluded that the results of enhanced solubility of TNZ using co-crystals is a clear indication of the potential for co-crystals to be used in the future for other poorly water-soluble drugs, considering that co-crystals are a safe and cost-effective approach.
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Ácidos Carboxílicos , Tinidazol , Rastreo Diferencial de Calorimetría , Cristalización , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Tinidazol/químicaRESUMEN
BACKGROUND: Solid dispersions are among the techniques successfully employed to enhance the dissolution of poorly water-soluble drugs. Microwave (MW)-assisted evaporative crystallization has been used to prepare solid dispersions of drugs and polymers. OBJECTIVES: The aim of the study was to investigate the solubility of apremilast (APM) in water by exploring the effect of MW-assisted solid dispersion technology. MATERIAL AND METHODS: In the present study, solid dispersions of APM, a poorly water-soluble drug, were prepared. The solid dispersions were prepared using the conventional method (CM) and the MW-based solvent evaporation technique. Microwave energy was used to enhance the solubility and dissolution rate of APM. The physical mixture and solid dispersions were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Apremilast tablets containing MW-assisted solid dispersions were prepared by the direct compression technique and compared with the marketed formulation (Aprezo tablets). RESULTS: The results obtained confirmed the conversion of crystalline APM to an amorphous form. The XRPD pattern of the MW-assisted formulation at a 2:1 ratio suggests the amorphous structure of APM within the formulation. Based on solubility studies results, Syloid® 244FP was selected as the best carrier. The dissolution study results suggested that the APM tablet prepared using MW-assisted solid dispersions at a 2:1 carrier/drug ratio improved the APM dissolution rate compared to the marketed formulation. CONCLUSIONS: Based on the results, it can be concluded that the MW-assisted solid dispersion technique may be an effective approach to enhancing the dissolution profile of other poorly water-soluble drugs.
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Microondas , Talidomida/análogos & derivados , Rastreo Diferencial de Calorimetría , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Comprimidos/químicaRESUMEN
BACKGROUND: Levocetirizine, active R (-) enantiomer of cetirizine, is an orally active and selective H1 receptor antagonist used medically as an anti-allergic. Allergic rhinitis is a symptomatic disorder of the nose induced by inflammation mediated by immunoglobulin E (IgE) in the membrane lining the nose after allergen exposure. OBJECTIVES: The purpose of the present study was to prepare rapidly disintegrating tablets of levocetirizine after its complexation with ß-cyclodextrin (ß-CD). MATERIAL AND METHODS: Levocetirizine-ß-CD complex tablets were prepared by direct compression technique using 3 synthetic superdisintegrants in different proportions. Development of the formulation in the present study was mainly based on the concentration of superdisintegrants and the properties of the drug. Nine batches of tablets were formulated and evaluated for various parameters: drug content, weight variation, water absorption ratio, wetting time, in vitro disintegration, hardness, friability, thickness uniformity, and in vitro dissolution. RESULTS: A Fourier-transform infrared spectroscopy (FTIR) study showed that there were no significant interactions between the drug and the excipients. The prepared tablets were good in appearance and showed acceptable results for hardness and friability. The in vitro disintegrating time of the formulated tablet batches was found to be 15-35 s percentage and the drug content of tablets in all formulations was found to be between 90-102%, which complied with the limits established in the United States Pharmacopeia. CONCLUSIONS: Complexation of levocetirizine with ß-CD significantly improves the solubility of the drug. The disintegration time of the tablets was decreased with an increase in superdisintegrant amount. The tablets (batch CPX5) had a minimum disintegration time of 20 s and 99.99% of the drug was released within 10 min.
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Cetirizina , Química Farmacéutica , Administración Oral , Cetirizina/química , Dureza , Solubilidad , ComprimidosRESUMEN
BACKGROUND: Nevirapine, an antiviral drug, is a potent reverse transcriptase inhibitor (NNRTI). It is used in combination with nucleoside analogues for treatment of HIV type-1 (HIV-1) infection and AIDS. Nevirapine is a BCS class II drug which shows dissolution rate limited absorption. OBJECTIVES: The aim of the present research was to provide a fast dissolving solid dispersion of nevirapine. MATERIAL AND METHODS: The solubility of nevirapine was initially determined individually in four hydrotropic agents - namely urea, lactose, citric acid and mannitol - at a concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. The highest solubility was obtained in the 40% citric acid solution. Then different combinations of 2 and 3 hydrotropic agents in different ratios were used to determine solubility, so that the total concentration of hydrotropic agents was always 40%. RESULTS: The highest solubility was obtained in a solution of lactose and citric acid at the optimum ratio of 15:25. This optimized combination was utilized in preparing solid dispersions by a common solvent technique using distilled water as a solvent. The solid dispersions were evaluated for XRD, DSC and FTIR to show no drug-hydrotrope interaction. CONCLUSIONS: It was concluded that the concept of mixed hydrotropic solid dispersion is a safe, novel and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs by dissolving the drug in a nonionized form. The enhancement in solubility of nevirapine using hydrotropy is a clear indication of its potential to be used in the future for other poorly water-soluble drugs in which low bioavailability is a major concern.
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Nevirapina/química , Disponibilidad Biológica , Ácido Cítrico/química , Lactosa/química , Manitol/química , Nevirapina/farmacocinética , Solubilidad , Urea/químicaRESUMEN
In the recent past, proteolysis-targeting chimera (PROTAC) technology has received enormous attention for its ability to overcome the limitations of protein inhibitors and its capability to target undruggable proteins. The PROTAC molecule consists of three components, a ubiquitin E3 ligase ligand, a linker, and a target protein ligand. The application of this technology is rapidly gaining momentum, especially in cancer therapy. In this review, we first look at the history of degraders, followed by a section on the ubiquitin proteasome system (UPS) and E3 ligases used in PROTAC development. PROTACs are dependent on the UPS for degradation of target proteins. We further discuss the scope and design of degraders and mitigation strategies for overcoming the hook effect seen with degraders. As PROTACs do not follow Lipinski's 'Rule of 5', these molecules face drug metabolism and pharmacokinetic challenges. A detailed section on absorption, distribution, metabolism, and excretion of degraders is provided wherein we discuss methodologies and strategies to surmount the challenges faced by these molecules. For understanding PROTAC-mediated degradation, the characterization and measurement of protein levels in cells is important. Currently used techniques and recent advancements in assessment tools for degraders are discussed. Furthermore, we examine the challenges and emerging technologies that need to be focused on in order to competently develop potent degraders. Many companies are working in this area of emerging new modality and a few PROTACs have already entered clinical trials; the details of the trials are included in this review.
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Complejo de la Endopetidasa Proteasomal , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Ligandos , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas/metabolismoRESUMEN
Efavirenz (EFZ) is a biopharmaceutics classification system (BCS) Class-II, first-line antiretroviral (ARV) drug. However, its utility through the oral route is restricted by its poor solubility. The objective of this study was to formulate EFZ-loaded binary-mixed micelles as a potential carrier for oral administration of EFZ. Rubingh's regular solution theory was used to determine the interaction behavior of the two components (Cremophor RH 40 and Phospholipon 80H) and of the mixed micelles and synergistic behavior was confirmed. The mixed miceller system was formulated using solvent evaporation method and a 32 factorial design was used for the optimization of selected independent variables. Miceller systems were further characterized in terms of morphology, particle size, zeta potential, percent entrapment efficiency, and drug loading. Fourier transform infrared and differential scanning calorimetry measurements confirmed the entrapment of EFZ in the micelles. The optimized formulation presented desirable qualities viz., nanometric size (17.27 ± 0.079), high entrapment efficiency, and good colloidal stability. The prepared optimized micelles can be potential carriers for EFZ in ARV therapies.
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Portadores de Fármacos , Micelas , Alquinos , Benzoxazinas , Ciclopropanos , Polímeros , SolubilidadRESUMEN
The objective of the current study was to develop new cocrystals of Apixaban (APX) to improve its solubility and permeability. The molecular interaction between APX and caffeine (CFFN) was further studied by Raman spectroscopy. The results of all eight studied conformers revealed that the synthesized APX-CFFN cocrystals had the highest solubility and permeability. The water solubility and permeability of APX in the cocrystal were simultaneously enhanced as compared with pure APX in the physiological pH environment (pH 6.8 and pH 7.4). The X-ray diffraction analysis revealed that the cocrystal has a component molar ratio of 1:1. This was dominated by a three-dimensional hydrogen bonding supramolecular structure. The in vivo pharmacokinetic (PK) study indicated that the mean area under curve (AUC) of APX from the synthesized cocrystal was enhanced more than three-folds than the pure APX. Tablets of APX and APX-CFFN cocrystals were prepared using direct compression method and evaluated for in vitro dissolution profile in phosphate buffers (pH 6.8 and pH 7.4). Computational investigations with molecular dynamics simulations also supported the formation of stable cocrystals. The drug release of APX from the tablets was considerably increased when compared with the pure APX in both pH conditions and it was found to increase with an increase in media pH. The present investigation represents an alternative approach for optimizing physicochemical and PK properties of Biopharmaceutical Classification System class-III drugs without changing its molecular structure and intrinsic bioactivities.
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Simulación de Dinámica Molecular , Pirazoles/química , Pirazoles/farmacocinética , Piridonas/química , Piridonas/farmacocinética , Animales , Química Física , Pollos , Cristalografía por Rayos X , Composición de Medicamentos , Concentración de Iones de Hidrógeno , Masculino , Estructura Molecular , Permeabilidad , Ratas , Ratas Wistar , Solubilidad , Distribución TisularRESUMEN
For routine monitoring of pesticides, a multiresidue analysis through solid-phase extraction technique and using high-performance liquid chromatography (HPLC) in cotton seed cake (CSC) has been developed. Extraction of fortified samples was carried out with aqueous acetone under vacuum. The concentrated extract was loaded onto the solid-phase extraction units, preconditioned with acetonitrile. The extraction units were then washed with hexane and finally eluted with acetonitrile. The pesticide residues were determined using a multiresidue method by reversed-phase HPLC. The average percentage recoveries were found to range between 65.47% and 110% at spiking levels of 10 to 40 mg/kg. The method developed shows a healthy rate of recovery and can successfully be utilized for the extraction and screening of neonicotinoid residues in CSC. The detection limits for imidacloprid, acetamiprid, and thiacloprid using this method were found to be 5, 10, and 20 mg/kg, respectively.
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Anabasina/análisis , Cromatografía Líquida de Alta Presión/métodos , Residuos de Plaguicidas/análisis , Extracción en Fase Sólida/métodos , Gossypium , India , Límite de DetecciónRESUMEN
AIM: The study was undertaken to find out the changes in biochemical and hormonal profile during transition period in single- and twin-bearing Beetal goats. MATERIALS AND METHODS: Beetal goats are reared in North India for milk and meat purposes, popularly called poor man's cow, serving as a source of livelihood. The present study was conducted on Beetal goats, maintained at a goat farm, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, for characterization of plasma biochemical and hormonal changes during transitional phase in pregnant goats carrying single and twin fetus. The animals selected were expected to have parturition at the same time, to avoid environmental variation effects, and divided into two groups: Group 1 (carrying single fetus, n=14) and Group 2 (twin fetus, n=6). Blood samples were collected from goats prepartum (-30 days and -15 days), 0 day, and postpartum +15 days and +30 days, and plasma was separated for the analysis of biochemical metabolites and hormones by commercially available kits. RESULTS: Analysis of data revealed a significant decrease in triglyceride and cholesterol concentration during postpartum days. A significant increase in alanine aminotransferase (ALT) concentration was observed at the day of parturition. Furthermore, there was a significant (p≤0.05) decrease in ALT and aspartate aminotransferase concentration in goats at the 15th day and 30th day after parturition in both groups. A significant (p≤0.05) lower concentration of total protein and globulins was observed during late pregnancy and on the day of parturition, with a subsequent elevation during postpartum period (15 days and 30 days). Progesterone concentration was highest at -30 days prepartum and decreased sharply at parturition and thereafter postpartum, both in single- and twin-bearing goats. Progesterone level was lower in twin-bearing goats as compared to single-bearing goats at 0 day and postpartum days. No significant changes were observed in sodium, potassium, and chloride concentration during transitional period in goats. CONCLUSION: Transition period blood metabolite profile changes due to physiological need of mother and fetus were more prominent in metabolites regulating energy requirements and in goats bearing twin fetus.
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Purpose: The objective of this work was to formulate casein (CAS) nanocarriers for the dissolution enhancement of poorly water soluble drug celecoxib (CLXB). Methods: The CLXB loaded CAS nanocarriers viz., nanoparticles, reassembled CAS micelles and nanocapsules were prepared using sodium caseinate (SOD-CAS) as a carrier to enhance the solubility of CLXB. The prepared formulations were characterized for particle size, polydispersity index, zeta potential, percentage entrapment efficiency, and surface morphology for the selection of best formulation. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray powder diffraction study was used to for the confirmation of encapsulation of CLXB. Further,in vitro drug dissolution, ex-vivo permeation studies on chicken ileum and stability studies were carried out. Results: The CLXB loaded casein nanoparticles (CNP) (batch A2) showed a particle size diameter 216.1 nm, polydispersity index 0.422 with percentage entrapment efficiency of 90.71% and zeta potential of -24.6 mV. Scanning electron microscopy of suspension confirmed globular shape of CNP. Thein vitro release data of optimized batch followed non Fickian diffusion mechanism. The ex vivo permeation studies on chicken ileum of CLXB loaded CNP showed permeation through mucous membrane as compared to pure CLXB. The apparent permeability of best selected freeze dried CLXB loaded CNP (batch A2) was higher and gradually increased from 0.90 mg/cm2 after 10 min to a maximum of 1.95 mg/cm2 over the subsequent 90 min. A higher permeation was recorded at each time point than that of the pure CLXB. Conclusion: The study explored the potential of CAS as a carrier for solubility enhancement of poorly water soluble drugs.
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BACKGROUND: The progression of fungal infections can be rapid and serious due to compromising with immune function. They may cause liver damage, affect estrogen levels or may cause allergic reactions. Oxiconazole nitrate (OXZN) is a broad spectrum commonly used antifungal drug. It acts by erogosterol biosynthesis inhibition, which causes lysis of the fungal cell membrane because of changes in both membrane integrity and fluidity and direct membrane damage of fungal cells. However, its poor water solubility and short half-life (3-5 h) limit its applications. OBJECTIVE: This study aimed to develop and evaluate OXZN-loaded nanostructured lipid carrier (NLC) to improve its solubility and prolong its release for the treatment of fungal infection via topical administration. METHOD: OXZN-NLC was prepared by ultrasonication method using 32 full factorial design. Glyceryl monostearate (GMS) (X1) and oleic acid (X2) were used as independent variables and particle size and percentage entrapment efficiency (% EE) as dependent variables. The OXZN-NLCs were characterized for particle size, particle morphology and entrapment efficiency. RESULTS: The mean diameter of optimized OXZN-NLCs was found to be 124 ± 2 nm. Spherical shape and size were confirmed using scanning electron microscopy (SEM). Skin deposition study showed about 82.74% deposition as compared with the marketed formulation that showed 68.42% deposition. The developed NLCs show a sustained release pattern and high drug disposition in the infected area. CONCLUSION: OXZN-NLC could be a potential alternative for the treatment of topical fungal infection after clinical evaluation in near future.
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Antifúngicos/administración & dosificación , Portadores de Fármacos/administración & dosificación , Imidazoles/administración & dosificación , Nanoestructuras/administración & dosificación , Absorción Cutánea , Geles , Glicéridos/administración & dosificación , Humanos , Micosis/tratamiento farmacológico , Ácido Oléico/administración & dosificación , Piel/metabolismoRESUMEN
BACKGROUND: Buspirone Hydrochloride is an anxiolytic agent and serotonin receptor agonist belonging to azaspirodecanedione class of compounds used in the treatment of anxiety disorders. It has short half-life (2-3h) and low oral bioavailability (4%) due to extensive first pass metabolism. OBJECTIVE: The nasal mucosa has several advantages viz., large surface area, porous endothelial membrane, high blood flow, avoidance of first-pass metabolism and ready accessibility that lead to faster and higher drug absorption. Keeping these facts in mind, the objective of the present study was to develop Buspirone hydrochloride loaded niosomal in-situ nasal gel. METHODS: Buspirone hydrochloride niosomal in situ nasal gel was formulated, optimized and evaluated with the objective to deliver drug to the brain via intranasal route. Niosomes were prepared by thin film evaporation method and optimized using32 factorial design. Niosomes were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. Buspirone hydrochloride loaded niosomes were further incorporated into Carbopol 934P and HPMC K4M liquid gelling system for the formation of in situ gel. The resultant solution was assessed for various parameters, viz., gelling time, gelling capacity, viscosity at pH 5 and pH 6. RESULTS: The vesicle size of all niosomal suspension batches ranges between 168.3 -310.5 nm. The vesicle size of optimized niosomal suspension F5 batch is 181.9±0.36nm. For F5 batch, the value of zeta potential was found to be -15.4 mV; this specifies that prepared niosomes have sufficient surface charge to prevent aggregation of the vesicles. % entrapment efficiency for all batches was found in the range 72.44±0.18% to 87.7±0.66%. The cumulative percent release of niosomal suspension ranges from 66.34±0.39 to 84.26±0.26%. Ex vivo permeation of Buspirone hydrochloride through the sheep nasal mucosa showed that 83.49% w/w drug permeated after 8 h. The SEM and Zeta potential studies showed the formation of stable vesicles. CONCLUSION: Thus, the application of niosomes proved the potential for intranasal delivery of Buspirone hydrochloride over the conventional gel formulations. Overall intranasal drug delivery for Buspirone hydrochloride has been successfully developed.
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Trastornos de Ansiedad/tratamiento farmacológico , Encéfalo/metabolismo , Buspirona/química , Portadores de Fármacos/química , Liposomas/química , Agonistas de Receptores de Serotonina/química , Administración Intranasal , Animales , Buspirona/administración & dosificación , Química Farmacéutica , Colesterol/química , Liberación de Fármacos , Geles , Humanos , Concentración de Iones de Hidrógeno , Mucosa Nasal/metabolismo , Tamaño de la Partícula , Permeabilidad , Agonistas de Receptores de Serotonina/administración & dosificación , Ovinos , ViscosidadRESUMEN
BACKGROUND: Low aqueous solubility is a major problem faced with new drug molecules. The purpose of this research was to provide a fast dissolving oral dosage form of Gliclazide (GLZ) using the concept of mixed hydrotropy. The recent patents on Adenosine (US20140107059A1), Growth hormone releasing factor peptide (EP0984788A1) and Paclitaxel (WO2002030466A2) helped in selecting the hydrotropes. METHODS: Solubility of GLZ was determined individually in sodium salicylate, nicotinamide, lactose, sodium acetate, urea, trisodium citrate and sodium benzoate. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope amount, mixed hydrotropic agents were used. RESULTS: Highest solubility was obtained in 25:15 ratio of sodium salicylate and sodium benzoate. This optimized combination was utilized in the preparation of solid dispersions which were evaluated for Xray diffractometry, Differential Scanning Calorimetry (DSC) and Fourier-transform infrared to show no drug-hydrotropes interaction. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus. CONCLUSION: The batch G3 tablets showed 86% cumulative drug release within 14min with in vitro dispersion time of 33sec. It was concluded that the enhancement in solubility of GLZ is a clear indication of the potential of mixed hydrotropy which is a novel, safe and cost-effective technique to be employed for other poorly water-soluble drugs having low bioavailability.
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Liberación de Fármacos , Gliclazida/administración & dosificación , Gliclazida/química , Patentes como Asunto , Solubilidad , Administración Oral , Liberación de Fármacos/efectos de los fármacos , Gliclazida/farmacología , Técnicas In Vitro , Solubilidad/efectos de los fármacos , ComprimidosRESUMEN
Proniosomes are the new generation provesicular drug delivery system of non-ionic surfactant, lecithin and cholesterol which upon reconstitution get converted into niosomes. The objective of current study was to develop stable and sustain transdermal delivery system for lornoxicam. Lornoxicam-loaded topically applied proniosomal gel was formulated, optimized, and evaluated with the aim to deliver drug transdermally. Lornoxicam-loaded proniosomal gels were prepared that contained Lutrol F68 and lecithin as surfactants, cholesterol as a stabilizer, and minimal amount of ethanol and trace water. The resultant lornoxicam-loaded proniosomal gel were assessed for stability and the proniosomes-derived niosomes were characterized for morphology, size, zeta potential, and entrapment efficiency, which revealed that they were suitable for skin application. The coacervation phase separation technique was used in formulation of lornoxicam proniosomal gel and the gel was further assessed for in vitro permeation of lornoxicam through the freshly excised rat skin and the cumulative permeation amount of lornoxicam from proniosome, all exhibited significant increase as compared to 1.0 % lornoxicam-loaded pure gel. The optimized F5 batch had shown maximum entrapment efficiency up to 66.98 %. It has shown sustained drug release for more than 24 h. The skin permeability of proniosomal gel was found to be 59.73 %. The SEM and zeta potential studies showed formation of good and stable vesicles. Thus, proniosomes proved to have better potential for transdermal delivery of lornoxicam over conventional gel formulations.
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Sistemas de Liberación de Medicamentos/métodos , Liposomas/química , Piroxicam/análogos & derivados , Administración Cutánea , Animales , Colesterol/química , Liberación de Fármacos , Estabilidad de Medicamentos , Geles/química , Lecitinas/química , Liposomas/ultraestructura , Masculino , Tamaño de la Partícula , Piroxicam/administración & dosificación , Piroxicam/química , Piroxicam/farmacocinética , Polietilenglicoles/química , Ratas , Absorción Cutánea , Propiedades de SuperficieRESUMEN
AIM AND BACKGROUND: Pregabalin (PRG), an analog of gamma-aminobutyric acid, reduces the release of many neurotransmitters, including glutamate, and noradrenaline. It is used for the treatment of epilepsy; simple and complex partial convulsion. The present research work aims to ensure a high drug absorption by retarding the advancement of PRG formulation through the gastrointestinal tract. The work aims to design a controlled release PRG formulation which is administered as liquid and further gels in the stomach and floats in gastric juice. MATERIALS AND METHODS: In situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methylcellulose (HPMC) K100M, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, drug content, in vitro gelling studies, gel strength, and in vitro drug release. The final formulation was optimized using a 3(2) full factorial design. RESULTS: The formulation containing 2.5% w/v sodium alginate and 0.2% w/v calcium chloride were considered optimum since it showed minimum floating lag time (18 s), optimum viscosity (287.3 cps), and gel strength (4087.17 dyne/cm(2)). The optimized formulation follows Korsmeyer-Peppas kinetic model with n value 0.3767 representing Fickian diffusion mechanism of drug release. CONCLUSION: Floating in situ gelling system of PRG can be formulated using sodium alginate as a gelling polymer and calcium chloride as a complexing agent to control the drug release for about 12 h for the treatment of epilepsy.
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Low aqueous solubility is a major problem faced during formulation development of new drug molecules. Lurasidone HCl (LRD) is an antipsychotic agent specially used in the treatments of schizophrenia and is a good example of the problems associated with low aqueous solubility. Lurasidone is practically insoluble in water, has poor bioavailability and slow onset of action and therefore cannot be given in emergency clinical situations like schizophrenia. Hence, purpose of this research was to provide a fast dissolving oral dosage form of Lurasidone. This dosage form can provide quick onset of action by using the concept of mixed hydrotropy. Initially, solubility of LRD was determined individually in nicotinamide, sodium citrate, urea and sodium benzoate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope concentration mixed hydrotropic agents were used. Highest solubility was obtained in 15:20:5 ratio of Nicotinamide + sodium benzoate + sodium citrate. This optimized combination was utilized in the preparation of solid dispersions by using distilled water as a solvent. Solid dispersions were evaluated for X-ray diffraction, differential scanning calorimetry and Fourier-transform infrared to show no drug-hydrotropes interaction has occurred. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus. The batch L3 tablets show 88% cumulative drug release within 14 min and in vitro dispersion time was 32 min. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs. The miraculous enhancement in solubility and bioavailability of Lurasidone is clear indication of the potential of mixed hydrotropy to be used in future for other poorly water-soluble drugs in which low bioavailability is a major concern.
RESUMEN
AIMS AND BACKGROUND: Donepezil (DNZ) is a centrally acting reversible acetyl cholinesterase inhibitor. The main therapeutic use of donepezil is in the treatment of Alzheimer's disease. The present research work pertains to the preparation of transdermal patches of donepezil with the objective to improve its patient compliance, therapeutic efficacy and to reduce the frequency of dosing and side effects as well as to avoid its extensive first pass metabolism. The recent patents on Rivastigmine (WO2013150542A2), Xanomeline (US5980933A) and Propentofylline (CA2255580A1) helped in selecting the drug and polymers. MATERIALS AND METHODS: The transdermal patches were prepared using various polymers in combination with the plasticizer and penetration enhancers. The physicochemical parameters like folding endurance, thickness, drug content, content uniformity, moisture absorption, weight variation, and drug permeation studies of the optimized patches were studied. RESULTS: The system containing Eudragit S -100, Eudragit E -100 and HPMC as matrix forming agent and glycerine as plasticizer was the best formulation. The in vitro release data was treated with kinetic equations and it followed zero order release. The diffusion study was carried out using rat skin showed 89% drug was released within 72 hours. Tween-80 (0.83 % w/w) was found to be the best among all penetration enhancers. All the transdermal patches had the desired physical properties like tensile strength, folding endurance, flatness and water vapor transmission rate etc. CONCLUSION: The study concluded that that transdermal patch can extend the release of donepezil for many hours and also ensure enhanced bioavailability, further it also helps in avoiding the first pass effect.
Asunto(s)
Química Farmacéutica/métodos , Indanos/síntesis química , Indanos/metabolismo , Piperidinas/síntesis química , Piperidinas/metabolismo , Parche Transdérmico , Administración Cutánea , Animales , Donepezilo , Evaluación Preclínica de Medicamentos/métodos , Indanos/administración & dosificación , Piperidinas/administración & dosificación , Ratas , Absorción Cutánea/efectos de los fármacos , Absorción Cutánea/fisiologíaRESUMEN
INTRODUCTION: Solid lipid nanoparticles (SLNs) are the new generation of submicron sized lipid emulsions where liquid lipid (oil) has been substituted by solid lipid. Lipids used in the formulation are safe, stable and biodegradable in nature. SLNs offer various advantages for topical drug delivery like ability of deposition into skin with the reduced systemic exposure and reduced local side-effects along with providing sustained release of drug. Mometasone furoate (MF) is a topical glucocorticoid having anti-inflammatory, anti-pruritic, anti-hyper proliferative activity. Owing to these properties it is recommended in chronic inflammation and psoriasis. In market, MF cream and lotion (0.1%) are available, which show slight skin irritation, burning and common side-effects due to steroids. EXPERIMENTAL: To overcome the shortcomings of conventional formulations, there is a need to develop a novel formulation that can reduce these side-effects and show maximum desired effects. Thus, SLN of MF can be prepared, which would help in increasing skin deposition as well as provide sustained release. In this study, SLNs were prepared by solvent - injection method. RESULTS: The F8 batch had shown maximum entrapment up to55.59% and sustained drug release for more than 8 h. The skin permeability of SLN loaded gel was found to be 15.21times more than that of marketed cream. SLN loaded gel showed 83.52% of skin deposition which was 2.67 times more than marketed cream and 20 times more than plain drug loaded gel. The scanning electron microscopy and zeta potential study showed formation of good SLN dispersion. The stability study showed successful formation of stable SLNs. Thus, SLNs proved the potential for topical delivery of corticosteroid drug over the conventional formulations. EXPERIMENTAL: To overcome the shortcomings of conventional formulations, there is a need to develop a novel formulation that can reduce these side-effects and show maximum desired effects. Thus, SLN of MF can be prepared, which would help in increasing skin deposition as well as provide sustained release. In this study, SLNs were prepared by solvent - injection method.