RESUMO
Operations that involve the maxillofacial region often require intraoral incisions, and contamination of these wounds is common as a result of the presence of saliva, plaque, and food debris. Postoperative infection is therefore common. The aim of the study was to evaluate the clinical efficacy of an intraoral dressing material, Reso-Pac®, in improving postoperative comfort for patients and its effect on wound healing. One hundred patients who required removal of impacted mandibular third molars were recruited, and were randomised into two groups (50 in each). A standardised surgical technique was used for removal of the impacted teeth, and wounds were closed with sutures. Postoperatively, the study group was given Reso-Pac® dressing while the control group was not. Postoperative pain was measured using a visual analogue scale (VAS). Wound healing was assessed with the help of Landry's scale, and we also measured thermal sensitivity. Data were analysed using the paired t test. The results in the study group were significantly better than those in the control group (p<0.001). Reso-Pac® promoted wound healing and improved patients' comfort during the postoperative phase.
Assuntos
Ferida Cirúrgica , Bandagens , Humanos , Mandíbula , Saliva , Infecção da Ferida Cirúrgica , CicatrizaçãoRESUMO
Permeation enhancement of salicylic acid (SA) from supersaturated solutions formed using a 'molecular form' technique was investigated. In a conventional cosolvent technique, two solvents are used, one in which the drug is considerably more soluble than the other. Propylene glycol and water have been predominantly used as cosolvents to create supersaturation in skin permeation enhancement. In this paper, we report the use of buffer solutions with different pHs as media for producing different molecular forms. Supersaturated solutions were prepared using pH 8:pH 2 (80:20 v/v), which gave a nominal pH when mixed of around 5. Model silicone membranes and human skin were used. Hydroxypropyl methyl cellulose (HPMC) was employed to stabilise the supersaturated states. Stability data showed that while the SA supersaturated solutions without HPMC crystallised between 15 min and 46 h depending on the degree of supersaturation, the solutions with HPMC were stable for more than 2 months. The flux of SA increased with the degree of saturation for solutions prepared in a 80:20 buffer pH 8/buffer pH 2 mixture. Although the fluxes of SA with and without HPMC were similar both through silicone membrane and human skin, HPMC was found to be effective in increasing the stability of supersaturated solutions of SA.
Assuntos
Anti-Inflamatórios não Esteroides/química , Ceratolíticos/química , Ácido Salicílico/química , Silicones/química , Absorção Cutânea/fisiologia , Algoritmos , Anti-Inflamatórios não Esteroides/farmacocinética , Fenômenos Químicos , Físico-Química , Difusão , Cultura em Câmaras de Difusão , Humanos , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Ceratolíticos/farmacocinética , Membranas Artificiais , Permeabilidade , Soluções Farmacêuticas , Ácido Salicílico/farmacocinéticaRESUMO
In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. "Standardized" calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 microg cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 microg cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intralaboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required.
Assuntos
Técnicas de Laboratório Clínico/normas , Variações Dependentes do Observador , Técnicas de Laboratório Clínico/estatística & dados numéricos , Difusão , Cultura em Câmaras de Difusão/métodos , Cultura em Câmaras de Difusão/normas , Cultura em Câmaras de Difusão/estatística & dados numéricos , Internacionalidade , Controle de Qualidade , Padrões de Referência , Valores de Referência , Absorção Cutânea/fisiologiaRESUMO
One method of improving the bioavailability of a topical formulation is to add an appropriate solvent that will act as a solubilizer for the permeant and, at the same time, modify the barrier properties of the stratum corneum. It has proved very difficult to determine the precise mechanisms of action involved; this is complicated by the concurrent diffusion of the solvent and the permeant into the skin. Under these circumstances the barrier function may well be changing as a function of time as the solvent disrupts it. We have observed this phenomenon in a model silicone membrane system that we have chosen to study initially to avoid the complexity of the heterogeneous nature of skin and its inherent biological variability. Diffusion experiments were conducted using an established ATR-FTIR approach but the data interpreted using sophisticated chemometric approaches that allowed us to deconvolve the IR signals from the permeant, the solvent, and the membrane. Data are presented that show the concurrent diffusion of benzoic acid (permeant), octanol (solvent), and how the octanol modifies the characteristics of the silicone membrane. Initial data are then presented using human skin to show the power of the diffusion approach coupled to the data deconvolution technique.
Assuntos
Membranas Artificiais , Solventes/farmacocinética , Difusão/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Solubilidade/efeitos dos fármacos , Solventes/análise , Espectroscopia de Infravermelho com Transformada de Fourier/métodosRESUMO
The bulk crystallization of alpha-lactose monohydrate from aqueous solution by primary nucleation has been studied under controlled conditions of supersaturation, temperature, and pH. The induction times to nucleation were extremely long compared with those generally observed for other materials, even at the high supersaturations used in the experiment. As a result, it was necessary to stir the supersaturated solution vigorously to induce nucleation in a reasonable but still lengthy working time. Even then, nucleation only occurred to a limited extent, following which growth ceased for 8-10 h before resuming. After this period, growth recommenced but again slowed to a low rate after another 8 h. At this stage, the yield of product was low and in most cases the particles had achieved sizes close to the maximum noted. The yields increased with further crystallization time (22-72 h total from the recommencement of growth) to give, under high initial supersaturation conditions, amounts of product close to the theoretical value. For the most part, however, the particle size did not increase with this later increase in yield, showing only significant changes after the extremely long total crystallization times. It is proposed that these extreme properties result from the formation in solution by mutarotation of the anomer alpha-lactose, which inhibits nucleation as well as its previously observed influence on growth.
Assuntos
Lactose/química , Cristalização , Concentração de Íons de Hidrogênio , SoluçõesRESUMO
The dissolution kinetics of alpha-lactose monohydrate (alphaLM) single crystals were studied by a flow-cell method at different undersaturations. Linear dissolution profiles were obtained as a function of time for all the faces except the (010) face. The dissolution rates, obtained from these profiles, were anisotropic and varied considerably with undersaturation. At low undersaturations (0-2%), the order of dissolution rate was (110) > (100) > (011) = (110) > (010). This order changed with increasing undersaturation (>5%) to (011) >> (100) > (110) > (110) > (010). In alphaLM crystals in which lattice strain was induced by synchrotron X-irradiation, the rates of dissolution of all faces increased with increasing strain. The increase was less significant for the (011) faces than for the remainder. Under this constraint, the (010) face became the fastest dissolving one and the [011]face became the slowest one. The results of all experiments are explained on the basis that although dislocations may act as initiating dissolution centers at very low undersaturations, these sources rapidly give way to two-dimensional nucleation of randomly distributed dissolution sites as the undersaturation is increased. Under these conditions, which better reflect the normal dissolution processes of materials, bulk lattice strain plays the most significant role in defining the dissolution rate. The results show a potential route to the controlled engineering of the dissolution behavior of crystalline materials.
Assuntos
Lactose/química , Cristalização , Cinética , Lactose/efeitos da radiação , Conformação Molecular , Solubilidade , Temperatura , Difração de Raios X , Raios XRESUMO
The effect of a series of alcohols on the permeation of salicylic acid (SA) and benzoic acid (BA) through silicone membrane was evaluated, using Franz-type diffusion cells. Although permeants were applied at the same thermodynamic activity in all vehicles, the resulting fluxes were found to differ significantly. This was a consequence of the interactions between the vehicles and the membrane. The interactions between the vehicles and the membrane were further investigated using ATR-FTIR spectroscopy. With this technique, it was possible to identify two different diffusion processes when the membrane was pre-treated with buffer, whereas one single diffusion process was observed when the membrane was pre-soaked with the vehicle. The technique was successfully used to deconvolute the relative magnitude of partition and diffusion in the permeation process. It was shown that the permeation of both acids was affected by the effect of the vehicles on the diffusion coefficient and the partition coefficient in the silicone membrane. The solubility of the drug in the impregnated membrane was found to be proportional to the saturated solubility in the vehicle used to treat the membrane. The solubility of BA in the impregnated silicone membrane was twice that of SA.
Assuntos
Antifúngicos/química , Ácido Benzoico/química , Membranas Artificiais , Ácido Salicílico/química , Silicones , Solventes/farmacologia , Permeabilidade/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Permeation enhancement of ibuprofen from supersaturated solutions formed using the cosolvent technique was investigated using silicone as a model membrane. Hydroxpropyl methyl cellulose and hydroxpropyl-beta-cyclodextrin were used to stabilise the supersaturated states. Physical stability studies showed best results for low drug concentrations in a 40:60 propylene glycol/water cosolvent system. Variations in flux across model silicone membranes from saturated solutions were observed as the PG content was increased. The flux of IBU increased with the degree of saturation for solutions prepared in a 40:60 PG/water cosolvent mixture. HPMC and CD were found to be effective in enhancing the stability of supersaturated solutions of IBU. The mechanisms of action are different for the two additives and are discussed.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Ibuprofeno/administração & dosagem , beta-Ciclodextrinas , Ciclodextrinas , Difusão , Estabilidade de Medicamentos , Ibuprofeno/química , Ibuprofeno/farmacocinética , Lactose/análogos & derivados , Metilcelulose/análogos & derivados , Oxazinas , Permeabilidade , SolubilidadeRESUMO
Systematic investigations on the diffusion of ibuprofen (IBU) from supersaturated solutions through human epidermis are reported. Significant flux enhancement was obtained from supersaturated solutions compared to the saturated solution. Hydroxypropyl methylcellulose (HPMC), when used as an additive was found to be effective in maintaining the high activity state at high degrees of saturation (DS). The increase in the flux was proportional to the DS. In the presence of 2-hydroxypropyl-beta-cyclodextrin (CD) at DS 2 and 3 a lower flux was observed compared to HPMC. At DS 5 a higher flux enhancement was found suggesting that CD might act as a penetration enhancer at certain CD/drug ratios. Studies on the mechanism of stabilisation of HPMC and CD on IBU crystallisation from supersaturated systems showed that HPMC acts as a growth inhibitor and habit modifier whereas CD does not influence the crystallisation process.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Ciclodextrinas/farmacologia , Ibuprofeno/farmacocinética , Lactose/análogos & derivados , Lactose/farmacologia , Metilcelulose/análogos & derivados , Metilcelulose/farmacologia , Pele/metabolismo , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina , Cristalização , Difusão , Humanos , Ibuprofeno/administração & dosagem , OxazinasRESUMO
The influence of hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG400) on the crystallization of hydrocortisone acetate (HA) was studied. Supersaturation was created by the cosolvent technique. Spontaneous nucleation was observed when no polymer was used as the additive. In the presence of the polymer, nucleation was delayed. The nucleation time decreased with increasing supersaturation at a particular polymer concentration and increased with increasing polymer concentration at a particular supersaturation. Habit modification from a well-defined polar prismatic morphology to a wing-shaped morphology was observed when HPMC was used as the additive. The effect of PVP and PEG400 on the morphology of HA was less pronounced compared to the cellulose polymers. The mechanism of nucleation retardation by the polymers is explained in terms of association of HA with the polymer through hydrogen bonding. The growth may be inhibited by the hydrodynamic boundary layer, in which the polymers accumulate as well as by the adsorption of the polymer onto the crystal surface. The habit modification of HA by HPMC is due to different extents of adsorption on different faces of the crystal, the extent of which is dependent on the hydrogen bonding functional groups that are exposed at each face of the crystal.
Assuntos
Hidrocortisona/análogos & derivados , Hidrocortisona/química , Lactose/análogos & derivados , Metilcelulose/análogos & derivados , Cristalização , Géis , Ligação de Hidrogênio , Lactose/farmacologia , Metilcelulose/farmacologia , Oxazinas , Polietilenoglicóis/farmacologia , Povidona/farmacologiaRESUMO
The aim of this paper is to prepare and stabilise, in situ, colloidal microsuspensions of triclosan using the polymer, hydroxypropyl methylcellulose (HPMC). The suspensions were prepared from supersaturated solutions of triclosan. The cosolvent technique was used to create supersaturation. Propylene glycol and water were used as the cosolvents. The triclosan particles had a large needle-shaped morphology, when grown in the absence of the polymer. Moreover, the particles grew rapidly to sizes greater than 5 micrometer over a period of 7h. When HPMC was added, the particle sizes were in the range 90-250 nm depending on the amount of polymer present in the solutions. The stability of the solutions was evaluated over a period of 40 days during which the particle sizes did not vary. The results were consistent with the mechanism proposed by Raghavan et al. [Int. J. Pharm. 212 (2001b) 213].
Assuntos
Anti-Infecciosos/química , Metilcelulose/análogos & derivados , Triclosan/química , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Cristalização , Estabilidade de Medicamentos , Ligação de Hidrogênio , Derivados da Hipromelose , Metilcelulose/química , Tamanho da Partícula , Solubilidade , SuspensõesRESUMO
A systematic investigation on the influence of two cellulose polymers, methyl cellulose (MC) and hydroxypropyl cellulose (HPMC) on supersaturation and permeation of hydrocortisone acetate (HA) is reported. Diffusion of HA from a 0.5% Carbopol gel across a model silicone membrane was investigated using the Franz-cell technique. At constant polymer concentration, the flux increases proportionally with the degree of saturation up to 4.8x but decreases thereafter. For a particular degree of supersaturation (4.8x), the flux increases with the concentration of polymer up to 1% and decreases at higher concentrations. The behaviour is found to be consistent with crystallisation experiments. The results suggest that optimisation of supersaturation and polymer content is necessary to achieve both high permeation rates and inherent stability.
Assuntos
Celulose/análogos & derivados , Hidrocortisona/análogos & derivados , Metilcelulose/química , Celulose/química , Cromatografia Líquida de Alta Pressão , Difusão , Géis , Hidrocortisona/química , Membranas Artificiais , Permeabilidade , Silicones , Solubilidade , SolventesRESUMO
Permeation of hydrocortisone acetate (HA) from supersaturated solutions was studied across a model silicone membrane. Supersaturated solutions were prepared using the cosolvent technique with propylene glycol and water (or aqueous polymer solutions) as the cosolvents. In the absence of the polymer, the flux of HA was similar at all degrees of saturation and was not significantly different from the value obtained for a saturated solution. Flux enhancement, as a result of supersaturation, was observed with all the polymers. The flux increased with increasing polymer concentration, reached a maximum and decreased at higher polymer percentages. The amount of polymer required for maximum enhancement differed for each polymer. The decrease of flux at high polymer concentrations is attributed to changes in microviscosity and a marginal increase in solubility. The infrared spectroscopic and differential scanning calorimetry data suggest that HA-polymer interactions occurred through hydrogen bonding thus explaining the proposed mechanism of the anti-nucleant properties of the polymers.
Assuntos
Hidrocortisona/análogos & derivados , Hidrocortisona/farmacocinética , Membranas Artificiais , Polímeros , Tecnologia Farmacêutica , Transporte Biológico , Varredura Diferencial de CalorimetriaRESUMO
Supersaturation is a very useful method of enhancing the permeation of drugs across membranes such as skin, because unlike other methods, it does not interfere with the ultrastructure of the stratum corneum. Many drugs are able to form inclusion complexes with beta-cyclodextrins (beta-CDs) and this study investigates the anti-nucleating effects of these compounds on supersaturated solutions of diclofenac. The ability of various betaCDs to form inclusion complexes with diclofenac was assessed by measuring their saturated solubilities. Solutions containing hydroxypropyl beta-cyclodextrin (HPbeta-CD, with a molar substitution of 0.9) produced a 7.5-fold increase in the solubility of diclofenac, which suggested that a strong complex was formed between the two compounds. This association was characterized using differential scanning calorimetry. Permeation across silicone membranes of these saturated solutions of diclofenac in the presence of the different betaCDs produced similar flux values suggesting that the overall activity was also similar. The effect of different molar ratios of HPbeta-CD and diclofenac, and the anti-nucleating effect of HPbeta-CD (both on its own and in combination with a known anti-nucleant, hydroxypropylmethyl cellulose (HPMC)) on the diffusion of diclofenac across silicone membranes was investigated. HPbeta-CD appears to have a stabilizing effect on supersaturated solutions of diclofenac as a co-ingredient with HPMC.
Assuntos
Ciclodextrinas/farmacocinética , Diclofenaco/farmacocinética , beta-Ciclodextrinas , Ciclodextrinas/análise , Diclofenaco/análise , Permeabilidade/efeitos dos fármacos , Soluções Farmacêuticas/análise , Soluções Farmacêuticas/farmacocinética , Solubilidade/efeitos dos fármacosRESUMO
A novel diffusion cell has been constructed which allows study of membrane diffusion processes without the need for sampling of the receiver compartment, that is highly sensitive and, being based around a diode array spectrophotometer also allows for continuous, real-time recording of multi-species concentration changes in the receiving compartment. The system is controlled to operate isothermally (via a Peltier control system) at temperatures between 15 and 85 degrees C. To examine the performance of this novel design, the transfer of tetracaine from a preparation in PEG 400 (20% tetracaine in PEG 400) has been studied. The results have been used to determine flux, lag time and related parameters. The performance of the novel cell is compared with results from traditional Franz cell diffusion studies.