RESUMO
AIM: Thiocolchicoside (THC) is a drug under the category of BCS III. Due to its high molecular weight, it has poor oral bioavailability and low skin permeability. This study aims to find an alternative delivery method for THC that enhances its bioavailability through nasal application approach. In situ gels containing plain or liposomal THC with different combinations of Pluronic® F127 and PEG 400 were prepared. METHOD: Liposome formulations were prepared using the thin film hydration method and tested for their characterization such as for drug content, particle size, and zeta potential. In vivo pharmacokinetic parameters of formulations such as Cmax, Tmax, and AUC were tested on the rabbit model. The formulations were also scrutinized for their cell viability properties. RESULT: Formulation composition with 2% soybean phosphatidylcholine and 10 mg THC exhibited â¼94% entrapment efficiency, minimum particle size 101.32 nm, low polydispersity index 0.225 and +0.355 zeta potential. In situ liposomal dispersion containing 15% Pluronic® F127 turned into gel at nasal temperature. Cell lines were unharmed for 48 h. In situ liposomal gels showed 1.5x higher blood concentration than the control formula. CONCLUSION: In situ gels of liposomal THC formulations offer advantages over traditional nasal solutions, demonstrating comparable bioavailability to parenteral medication while also preserving the health of nasal mucosa cells.
Assuntos
Administração Intranasal , Disponibilidade Biológica , Colchicina , Géis , Lipossomos , Tamanho da Partícula , Poloxâmero , Polietilenoglicóis , Animais , Coelhos , Poloxâmero/química , Colchicina/administração & dosagem , Colchicina/análogos & derivados , Colchicina/farmacocinética , Polietilenoglicóis/química , Temperatura , Humanos , Masculino , Mucosa Nasal/metabolismo , Mucosa Nasal/efeitos dos fármacosRESUMO
The focus of the research was to overcome the limitations of metoclopramide (MTC) when administered intranasally. The aim was to improve its bioavailability, increase patient compliance, and prolong its residence time in the nasal cavity. MTC-loaded liposomes were prepared by applying the film hydration method. A study was conducted to determine how formulation variables affected encapsulation efficiency (EE %), mean particle size (MPS), and zeta potential (ZP). The MTC-liposomes were further loaded into the in situ gel (gellan gum) for longer residence times following intranasal administration. pH, gelling time, and in vitro release tests were conducted on the formulations produced. In vivo performance of the MTC-loaded in situ gels was appraised based on disparate parameters such as plasma peak concentration, plasma peak time, and elimination coefficient compared to intravenous administration. When the optimal liposome formulation contained 1.98% of SPC, 0.081% of cholesterol, 97.84% of chloroform, and 0.1% of MTC, the EE of MTC was 83.21%, PS was 107.3 nm. After 5 h, more than 80% of the drug was released from MTC-loaded liposome incorporated into gellan gum in situ gel formulation (Lip-GG), which exhibited improved absorption and higher bioavailability compared to MTC loaded into gellan gum in situ gel (MTC-GG). Acceptable cell viability was also achieved. It was found out that MTC-loaded liposomal in situ gel formulations administered through the nasal route could be a better choice than other options due to its ease of administration, accurate dosing, and higher bioavailability in comparison with MTC-GG.
Assuntos
Lipossomos , Metoclopramida , Coelhos , Humanos , Animais , Disponibilidade Biológica , Administração Intranasal , Náusea , Lipídeos , Géis , Tamanho da Partícula , Sistemas de Liberação de MedicamentosRESUMO
CONTEXT: Eplerenone is a member of antihypertensives used individually or in combination with other medicines. Eplerenone exhibits poor solubility and is considered a class II drug. OBJECTIVE: Increasing the solubility of eplerenone by using both liquid and solid self-emulsifying drug delivery systems as an alternative to its marketed tablet product. METHODS: Solubility studies of eplerenone were done with different oils, surfactants, and co-surfactants to determine which one has the highest solubility for eplerenone and determine the preference in the formulations of liquid self-emulsifying drug delivery system. The solidification process was carried out with the adsorption to solid carrier method. Optimal ratios of components were specified with the pseudo-ternary phase diagram technique. Self-emulsifying drug delivery system formulations were characterized in terms of chemical interaction, droplet size/distribution, crystallization behaviors, and rheological evaluation. In vitro drug release studies were conducted and compared to pure drugs and marketed products. RESULTS: The solubility screening results showed high solubility of EPL in triacetin (11.99 mg/mL) as oil, Kolliphor®EL (≈ 2.65 mg/mL), and Tween80 (≈ 1.91 mg/mL) as surfactant and polyethylene glycol 200 (PEG200) (≈ 8.50 mg/mL), dimethyl sulfoxide (≈ 7.57 mg/mL), TranscutolP (≈ 6.03 mg/mL) as co-surfactant, respectively. Rheology studies revealed that liquid self-emulsifying drug delivery formulations exhibited non-Newtonian pseudoplastic flow. CONCLUSION: Solid self-emulsifying drug delivery systems prepared with Aerosil and Neusilin have shown tremendous improvement in terms of eplerenone dissolution by releasing the entire dose with boosted effect within 5 and 30 min respectively compared to the marketed product and pure eplerenone (p < 0.05).
Assuntos
Sistemas de Liberação de Medicamentos , Tensoativos , Solubilidade , Eplerenona , Emulsões/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Tensoativos/química , Disponibilidade BiológicaRESUMO
Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations' inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19 nm, 82.38 nm, and 126.35 nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye.
Assuntos
Portadores de Fármacos , Nanopartículas , Humanos , Etabonato de Loteprednol , Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Anti-Inflamatórios/farmacologia , Córnea , Tamanho da PartículaRESUMO
AIM: Loteprednol etabonate (LE) is a new generation corticosteroid that is used for the treatment of inflammatory and allergic conditions of the eye. Therefore, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were attempted to improve transdermal LE delivery for the first time. METHODS: SLN and NLC were produced by hot homogenisation and ultrasonication technique. Their physical stability was monitored for 3 months of storage. Drug release and permeation of SLN and NLC through the porcine skin were investigated. RESULTS: It was determined that SLN and NLC mean particle size of 139.1 nm had a homogeneous particle size distribution (â¼0.169 PI) and the mean charge was -23.6. They were found to be stable both physically and chemically at room temperature. CONCLUSION: SLN and NLC formulations of LE can be stated among the systems that can be an alternative to conventional systems with fewer side-effects in the treatment of inflammatory problems.
Assuntos
Portadores de Fármacos , Nanopartículas , Lipídeos , Lipossomos , Etabonato de Loteprednol , Tamanho da PartículaRESUMO
Essential oils have a high volatility that leads to evaporation and loss of their pharmacological effect when exposed to the environment. The objectives of the present work were to prepare microcapsules with oregano essential oil by extrusion using sodium alginate as a shell material and non-ionic surfactant polysorbate 80 as an emulsifier to stabilize the emulsion. The present study was aimed to evaluate the physical parameters of microcapsules and to compare the influence of the amount of emulsifier and the essential oil-to-emulsifier ratio on the capsules' physical parameters and encapsulation efficiency; to our knowledge, the existing research had not yet revealed whether unstable emulsion affects the encapsulation efficiency of oregano essential oil. This study showed that increasing the emulsifier amount in the formulation significantly influenced encapsulation efficiency and particle size. Moreover, increasing the emulsion stability positively influenced the encapsulation efficiency. The emulsion creaming index depended on the emulsifier amount in the formulation: the highest creaming index (%) was obtained with the highest amount of polysorbate 80. However, the essential oil-to-polysorbate 80 ratio and essential oil amount did not affect the hardness of the microcapsules (p > 0.05). In conclusion, the obtained results could be promising information for production of microcapsules. Despite the fact that microencapsulation of essential oils is a promising and extremely attractive application area for the pharmaceutical industry, further basic research needs to be carried out.
Assuntos
Alginatos/química , Cápsulas/química , Emulsificantes/química , Emulsões/química , Óleos Voláteis/química , Origanum/química , Polissorbatos/química , Tamanho da PartículaRESUMO
The purpose of this study was to investigate the effect of formulation variables on properties related to critical functionality for their use in indomethacin buccal tablets. Chitosan (CH), carbopol (PAA), and hydroxypropyl methyl cellulose (HPMC) concentration and filler type were evaluated as parameters for describing tablet hardness, swelling index, indomethacin release, and mucoadhesion in controlled release buccal tablets. Moreover, a 32 full factorial design was employed to study the effect of each polymer ratio in CH and PAA combination, which significantly influenced characteristics. A slower indomethacin release and a considerably larger degree of swelling were found for different concentrations of PAA or CH (p < 0.05). The buccal tablets formed a continuous gel layer while in contact with the aqueous medium undergoing a combination of swelling and erosion. In vitro drug release in simulated saliva (pH 6.75) appears to occur both by diffusion and a swelling-controlled mechanism, exhibiting anomalous, Case II type transport or Super Case II type transport. The diluent present in all study samples, mannitol (MAN), spray-dried lactose (SDL), and microcrystalline cellulose (MC) were believed to contribute minimally to hydrogel formation and drug release regulation. The dissolution values for the three co-excipients were decreasing order mannitol, spray-dried lactose, and microcrystalline cellulose. In conclusion, the type and concentration of all polymers seem to change the functionality of buccal tablets and it seems important to understand and characterize these excipients to fully predict the drug release, mucoadhesion, and swelling of buccal tablets.
Assuntos
Excipientes , Indometacina , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Humanos , Solubilidade , ComprimidosRESUMO
Dihydroergotamine mesylate (DHE), ergotamine derivative, has been offered for clinical use to stop or treat symptoms of an emerging migraine as injection for more than a half century. It is shown that bioavailability of DHE greatly changes between the subjects and up to 99% of the orally absorbed dose may be cleared by first pass metabolism. The aim of this study was to design and optimize DHE fast-dissolving sublingual films for migraine treatment. For this purpose pullulan and maltodextrin was chosen as film-forming polymers and propylene glycol as plasticizer. For optimization process Box Behnken design was used. The formed films were free from air bubbles, cuttings, or cracks. Disintegration, mechanical strength and dissolution of films were compared. It is found that pullulan and maltodextrin formed films with the most desired properties at the concentration of 1.5% and 2%. The application of optimum formulation to rabbits showed that bioavailability of formulation is about 23.35% with a tmax 20 min. Due to this fast onset of action and higher bioavailability than oral administration, it is suggested that the polymer combinations of pullulan and maltodextrin formed successful films and were considered as an alternative dosage form for DHE in migraine therapy.
Assuntos
Di-Hidroergotamina/farmacocinética , Composição de Medicamentos/métodos , Excipientes/química , Vasoconstritores/farmacocinética , Administração Sublingual , Animais , Disponibilidade Biológica , Di-Hidroergotamina/administração & dosagem , Avaliação Pré-Clínica de Medicamentos , Liberação Controlada de Fármacos , Feminino , Glucanos/química , Injeções Intravenosas , Transtornos de Enxaqueca/tratamento farmacológico , Polissacarídeos/química , Coelhos , Solubilidade , Fatores de Tempo , Vasoconstritores/administração & dosagemRESUMO
Superficial fungal infections caused by Candida species are common skin diseases. Therefore, this study aimed to develop a new formulation containing oxiconazole nitrate, which is an azole group derivative for antifungal treatment, as a thermosensitive gel since there has been no literature study until now. MIC value of the novel thermosensitive formulation against three Candida species was calculated and time-dependent antifungal activity analysis was performed. Viscosity, transition temperature Tsol-gel (°C) and gelation time of the thermosensitive gel formulation were also determined in the viscometer. The measurements performed on the tensilometer device were analyzed for adhesion hardness and elongation percentages of the formulation. In the FT-IR spectrometer, the spectrum of solution and gel state was compared between 650 and 4000â¯cm-1 and it was found that there is no difference between them. It was found that the temperature is reversible on the formulation and did not cause any disruption of its components. Characterization parameters of the thermosensitive gel formulation containing oxiconazole nitrate and time-dependent activity against Candida species was observed to be the same as those of the solution containing only oxiconazole nitrate. MIC, MFC and time-dependent antifungal analysis did not show any particular difference between formulation and oxiconazole nitrate itself. Thermosensitive gel formulation containing oxiconazole nitrate was found to be effective on superficial fungal infections. We believe it is also appropriate for in vivo usage, but it is necessary to perform animal and human research. It is also needed to evaluate the formulation against other etiologic agents of superficial fungal infections.
RESUMO
Metoclopramide HCl (MTC) is commonly used for the management of gastrointestinal disorders. It has a short biological half-life and is usually administered four times daily to maintain effective concentrations throughout the day. The aim of this study is to develop sustained-release hydrophilic matrix tablet formulations of drug to achieve reproducible and predictable release rates, extended duration of activity, decreased toxicity, reduction of required dose, optimized therapy, and improved patient compliance. Hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose sodium (NaCMC), chitosan and Carbopol 981 were incorporated in the matrix system separately or in combinations as release controlling factor by direct compression technique. Compatibility among the formulation components was assessed by DSC and FTIR analysis. MTC release from matrix was evaluated by using the US Pharmacopeia dissolution apparatus II. All formulations met the criteria of pharmacopeial requirements. Dissolution studies show that polymer type and concentration are important parameters on drug release. Chitosan, carbopol and NaCMC formulations exhibited pH-dependent drug release profile whereas HPMC did not. All the formulations containing 1:1 ratio of HPMC and chitosan exhibited desired drug release showing that all active substance releases progressively in a period of whole dissolution time and therefore it can be regarded as worthy of consideration for the manufacture of sustained-release MTC product.
Assuntos
Metoclopramida/química , Polímeros/química , Comprimidos/química , Resinas Acrílicas/química , Carboximetilcelulose Sódica/química , Química Farmacêutica/métodos , Quitosana/química , Preparações de Ação Retardada , Composição de Medicamentos/métodos , Excipientes/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , SolubilidadeRESUMO
This research primarily focuses on the development of innovative topical nanoemulsions for etodolac, aimed at surmounting its inherent limitations. The preparation of etodolac nanoemulsions is accomplished through a combination of high shear homogenization and ultrasonication methods. The optimization of the formulation components is systematically conducted using the design of experiments methodology. The droplet size (DS), polydispersity index (PDI), and zeta potential (ZP) of the optimized formulation were assessed using the differential light scattering (DLS) technique. Surface morphology examinations were conducted using electron microscopy, while interactions between excipients and the drug were analyzed through FTIR analysis. Additionally, in vitro release and ex vivo permeability studies were carried out. Furthermore, anti-inflammatory activity was evaluated in the context of a carrageenan-induced paw edema model in rats. The DS, PDI, and ZP of the optimal formulation were 163.5 nm, 0.141, and -33.1 mV, respectively. The in vitro release profile was assessed as a sustained release by following a non-Fickian drug transport. The flux of etodolac nanoemulsions and coarse dispersions were 165.7 ± 11.7 µg/cm2 h and 59.7 ± 15.2 µg/cm2 h, respectively. Enhanced edema inhibition was observed at 13.4%, 36.5%, and 50.65% for the 6th, 8th, and 24th hours, respectively. Taken together, these results confirmed that nanoemulsions are promising carriers for the topical delivery of etodolac.
RESUMO
Ocular drug delivery methods are highly favored for boosting bioavailability, patient compliance, and lower adverse effects and dose frequency. In addition to preventing adverse effects from the active ingredient, the parts of drug delivery systems must be nontoxic and nonallergic as well. Mitochondrial toxicity test (MTT) and Hen's egg chorioallantois membrane (HET-CAM) assay are the most often utilized tests based on this dilemma. The toxicity of loteprednol etabonate loaded solid lipid nanoparticles, lipid nanostructured carriers, and nanoemulsion were compared. Oleic acid, Precirol®ATO5, and Pluronic® F68 were used in the preparation. Their toxicities were evaluated by using two different toxicity tests (MTT and HET-CAM). The results suggest that there are no significant differences between the HET-CAM and MTT assays. It is noteworthy that the HET-CAM assay offers a more cost-effective and environmentally friendly alternative to the MTT assay, as it does not require cell culture and generates less toxic waste. This information may be useful to consider when selecting between the two assays.
Assuntos
Galinhas , Olho , Animais , Feminino , Humanos , Membrana Corioalantoide , Sistemas de Liberação de Medicamentos , BioensaioRESUMO
Etodolac, a highly lipophilic anti-inflammatory drug, is widely used in rheumatoid arthritis usually at an oral dose of 200 mg twice daily. The commonest side effects during therapy with etodolac is generally gastrointestinal disturbances these are usually mild and reversible but in some patients are peptic ulcer and severe gastrointestinal bleeding. To eliminate these side effects and obtain high drug concentration at the application side, dermal application of etodolac seems to be an ideal route for administration. Hydrophilic gel formulations of etodolac were prepared with carboxymethylcellulose sodium. The effect of different terpenes (anethole, carvacrol, and menthol) as an enhancer on the percutaneous absorption of etodolac was also investigated. Permeation studies were carried out with unjacketed modified horizontal diffusion cells through cellulose membrane and rat skin. In vitro studies with cellulose membrane showed that all formulations presented the same drug release profile (p > 0.05). Ex vivo studies with excised rat skin revealed that etodolac was released and penetrated into rat skin quickly. Anethole, a hydrophobic terpene, enhanced the absorption of etodolac significantly (p < 0.05). This result is consistent with the fact that hydrophobic terpenes are effective on the percutaneous absorption of lipophilic drugs. Menthol and carvacrol, hydrophilic terpenes, did not enhance the absorption of etodolac. The lipophilicity of the enhancers seems an important factor in promoting penetration of etodolac through the skin. Since etodolac creates gastrointestinal disturbances, topical formulations of etodolac in gel form including 1% anethole could be an alternative.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Etodolac/farmacocinética , Absorção Cutânea , Terpenos/farmacologia , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Carboximetilcelulose Sódica/química , Celulose , Química Farmacêutica , Portadores de Fármacos/química , Etodolac/administração & dosagem , Excipientes/química , Géis/química , Interações Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Masculino , Membranas Artificiais , Permeabilidade , Ratos , Ratos WistarRESUMO
BACKGROUND: Anastomosis with tissue adhesives is an alternative method for conventional anastomosis. However, this method has several technical challenges. It requires the use of suture to prevent leakage into lumen and precise application onto all surfaces of the anastomosis site. To solve these problems, poloxamer 407 (P 407) was previously used as a stent. In this study, we made heparinized P 407 (h-P 407) as a new formula. We aimed to successfully use h-P 407 as a stent in sutureless anastomosis in a rat abdominal aorta model. METHODS: Sixty Sprague-Dawley rats were used. In the first group, end-to-end anastomoses were performed with suture; in the second and third groups, sutureless anastomoses were performed with 2-octyl cyanoacrylate. As an intraluminal stent, P 407 was used in the second group, and h-P 407 was used in the third group. Anastomosis time was measured. Lumen width, intimal hyperplasia, and foreign body reaction were assessed histologically. Velocity flow rates and vessel diameters were measured radiologically. Burst strength was measured, and the results were statistically evaluated. RESULTS: Sutureless anastomosis was more rapid than conventional anastomosis. Lumen width was narrower in the suture group. Inflammation and foreign body reaction were more severe in the suture group. There was no radiologic and biomechanical difference between the groups. We found that intimal hyperplasia was less in h-P 407 than in P 407. CONCLUSION: h-P407 can be successfully used as an intraluminal stent for sutureless microvascular anastomosis with tissue adhesives.
Assuntos
Heparina/farmacologia , Poloxâmero , Técnicas de Sutura/instrumentação , Suturas , Procedimentos Cirúrgicos Vasculares/métodos , Anastomose Cirúrgica/métodos , Animais , Anticoagulantes/farmacologia , Ratos Sprague-Dawley , Tensoativos , Adesivos Teciduais/farmacologia , Túnica Íntima/cirurgiaRESUMO
Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability. In this study, we developed a dissolving microneedle patch (MNP) made of polyvinylpyrrolidone, due to its high aqueous solubility and solubility enhancement properties, using a MNP design previously shown to be painless and simple to administer. DHE-loaded MNPs were shown to have a content uniformity of 108±9% with sufficient mechanical strength for insertion to pig skin ex vivo and dissolution within 2min. In vivo pharmacokinetic studies were carried out on hairless rats, and DHE plasma levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under curve (AUC) value after DHE delivery by MNP (1259±917ng/mL min) was not significantly different (p>0.05) as compared to subcutaneous injection, with a relative bioavailability of 97%. Also, appreciable plasma levels of DHE were seen within 5min for both delivery methods and tmax value of MNPs (38±23min) showed no significant difference (p>0.05) compared to subcutaneous injection (24±13min). These results suggest that DHE-loaded MNPs have promise as an alternative DHE delivery method that can be painlessly self-administered with rapid onset and high bioavailability.
Assuntos
Dor Aguda/tratamento farmacológico , Analgésicos não Narcóticos/administração & dosagem , Di-Hidroergotamina/administração & dosagem , Sistemas de Liberação de Medicamentos , Transtornos de Enxaqueca/tratamento farmacológico , Analgésicos não Narcóticos/química , Analgésicos não Narcóticos/farmacocinética , Animais , Disponibilidade Biológica , Di-Hidroergotamina/química , Di-Hidroergotamina/farmacocinética , Liberação Controlada de Fármacos , Injeções Subcutâneas , Masculino , Microinjeções , Agulhas , Povidona , Ratos Pelados , Ratos Sprague-Dawley , Pele/metabolismo , Solubilidade , SuínosRESUMO
There is a need for nasal drug delivery of metoclopramide HCI (MTC) in specific patient populations where the use of commercially available intravenous and oral dosage forms may be inconvenient and/or unfeasible. In this perspective, nasal dosage forms (solution, gel and lyophilized powder) of MTC were prepared by using a mucoadhesive polymer Carbopol 981 (CRB 981). The drug release studies of formulations were performed by using a modified horizontal diffusion chamber with cellulose membrane and excised cattle nasal mucosa as diffusion barriers. After the ex vivo experiments, the morphological appearances of the nasal mucosa were analyzed with the light microscopic studies. In vivo experiments were carried on sheep model. The release of MTC from solution and powder formulations was found higher than gel formulation (p < 0.05) and no severe damage was found on the integrity of nasal mucosa after ex vivo experiments. The penetration enhancing effect of dimethyl-beta-cyclodextrin (DM-beta-CD) used in powder formulations was observed in ex vivo and in vivo experiments. In contrast to in vitro and ex vivo experiments the nasal bioavailability of gel formulation was found higher than those of the solution and powder (p < 0.05) and might represent a promising novel tool for the systemic delivery of MTC.
Assuntos
Resinas Acrílicas/química , Metoclopramida/farmacocinética , Mucosa Nasal/metabolismo , Absorção/fisiologia , Animais , Disponibilidade Biológica , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/química , Antagonistas de Dopamina/farmacocinética , Avaliação Pré-Clínica de Medicamentos/métodos , Géis , Humanos , Concentração de Íons de Hidrogênio , Metoclopramida/administração & dosagem , Metoclopramida/sangue , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Permeabilidade , Pós , Ovinos , Soluções , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacocinéticaRESUMO
The objective of this study was to evaluate the in vitro and ex vivo percutaneous absorption of chlorpheniramine maleate (CPM) from different hydrogel formulations. Various concentrations of polymers, including hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC) and methyl cellulose (MC) were used in the hydrogel formulations. All experiments were conducted using cellulose dialysis membrane. The passive permeation of CPM was affected by the polymer concentrations. The effect of each polymer on the release rate of CPM was found to be statistically different (P<0.05). The formulation which exhibited maximum drug release through cellulose membrane was then used with other membranes namely polyurethane membrane, rat skin and human skin. The release rate of CPM from different membranes was found to be statistically different (P<0.05). Within the different diffusional barriers rat skin was found to be best alternative to human skin. It seems suitable the use of cellulose derivatives for topical application of CPM to obtain high therapeutic concentration at the application site. The synthetic membranes can be used to assess product performance in quality assurance but give little indication of its performance ex vivo.
Assuntos
Celulose/análogos & derivados , Clorfeniramina/química , Clorfeniramina/farmacocinética , Antagonistas dos Receptores Histamínicos H1/química , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Hidrogéis/química , Animais , Preparações de Ação Retardada , Diálise , Difusão , Estabilidade de Medicamentos , Humanos , Técnicas In Vitro , Masculino , Membranas Artificiais , Permeabilidade , Ratos , Ratos Sprague-Dawley , Absorção Cutânea , ViscosidadeRESUMO
Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to carry out an injection. The aim of this study was to develop a transdermal patch containing microneedles (MNs) coated with a peptide drug, salmon calcitonin (sCT), as an alternative to traditional subcutaneous and nasal delivery routes. Quantitative analysis of sCT after coating and drying onto microneedles was performed with a validated HPLC method. In vivo studies were carried out on hairless rats and serum levels of sCT were determined by ELISA. The AUC value of MNs coated with a trehalose-containing formulation (250 ± 83 ng/mL min) was not significantly different as compared to subcutaneous injections (403 ± 253 ng/mL min), but approximately 13 times higher than nasal administration (18.4 ± 14.5 ng/mL min). T(max) (7.5 ± 5 min) values for MN mediated administration were 50% shorter than subcutaneous injections (15 min), possibly due to rapid sCT dissolution and absorption by dermal capillaries. These results suggest that with further optimization of coating formulations, microneedles may enable administration of sCT and other peptides without the need for hypodermic injections.
Assuntos
Calcitonina/administração & dosagem , Materiais Revestidos Biocompatíveis , Portadores de Fármacos , Administração Intranasal , Animais , Disponibilidade Biológica , Calcitonina/sangue , Calcitonina/química , Calcitonina/farmacocinética , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Desenho de Equipamento , Injeções Intradérmicas , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Microinjeções , Miniaturização , Agulhas , Ratos , Ratos Pelados , Ratos Sprague-Dawley , Solubilidade , Tecnologia Farmacêutica/métodos , Adesivo TransdérmicoRESUMO
First-pass metabolism can be overcome by sublingual drug delivery, and quick drug entry into the systemic circulation can be obtained. In certain diseases such as migraine therapy, taking fast pharmacological response is an important criteria. In this study, zolmitriptan sublingual tablets were prepared by direct compression method using different mucoadhesive polymers such as hydroxypropyl methyl cellulose, chitosan and sodium carboxy methyl cellulose at a concentration range of 0.5-5% to reduce flushing action of saliva and provide enough time for drug to be absorbed. Tablets were evaluated for the physical properties, and optimum formulations were chosen for in vivo studies to carry on sheep model. The tablets disintegrated rapidly, and dissolution tests revealed that zolmitriptan was dissolved from the formulation within the compendial limits. This especially showed us that the concentration range of polymers is in acceptable limit. It was also concluded that microcrystalline cellulose, spray-dried lactose and sodium starch glycolate are the appropriate excipient and formulated in good proportions. In vivo studies indicated that formulation containing 5% chitosan has the maximum C(max) and AUC and minimum t(max) values (p<0.05). As a result, sublingual tablet administration of zolmitriptan formulated with appropriate excipients and especially with chitosan seems promising alternative to traditional routes.
Assuntos
Composição de Medicamentos/métodos , Excipientes/química , Oxazolidinonas/química , Agonistas do Receptor 5-HT1 de Serotonina/química , Triptaminas/química , Administração Sublingual , Animais , Fenômenos Químicos , Força Compressiva , Sistemas de Liberação de Medicamentos , Feminino , Lactose/química , Oxazolidinonas/administração & dosagem , Oxazolidinonas/sangue , Oxazolidinonas/farmacocinética , Permeabilidade , Polímeros/química , Agonistas do Receptor 5-HT1 de Serotonina/administração & dosagem , Agonistas do Receptor 5-HT1 de Serotonina/sangue , Agonistas do Receptor 5-HT1 de Serotonina/farmacocinética , Ovinos , Solubilidade , Comprimidos , Triptaminas/administração & dosagem , Triptaminas/sangue , Triptaminas/farmacocinéticaRESUMO
A novel oral controlled delivery system for benzydamine hydrochloride (BN) was developed and optimized. Hydrophilic matrix tablets of BN were prepared by using hydroxypropylmethylcellulose (HPMC) and chitosan as polymer substance to achieve required sustained release profile. The matrix tablets were prepared both direct compression and wet granulation method. The influence of matrix forming agents and binary mixtures of them on BN release was investigated. The formulated tablets were characterized by hardness, friability, thickness, weight variation and in vitro drug release. The formulated tablets had acceptable physicochemical characters. The quantity of BN present in the tablets and the release medium were estimated by a simple, sensitive, rapid and validated HPLC method. The dissolution results show that increased amount of polymer resulted in reduced and extended drug release. F7 formulation containing 12.5% HPMC and 12.5 % chitosan with direct compression method is the optimum formulation due to its better targeting profile in terms of release. Higuchi (diffusion) and Hixon-Crowell (erosion) kinetic profiles were achieved and this codependent mechanism of drug release was established. This formulation may provide an alternative for oral controlled delivery of BN and be helpful in the future treatment of primary normoreactive types of inflammation.