Therapeutic Intervention of Aloe Gel Containing Nano-Sized and Micron-Sized Silver Sulfadiazine Gel on Second-Degree Burn: A Comparative Study.

The current work focuses on the formulation development, optimization, and in vivo assessment of nano-sized silver sulfadiazine ( nSSD) and micron-sized silver sulfadiazine ( mSSD) topical gel composed of Aloe vera gel ( Aloe gel) and Carbopol 940 for the management of second-degree burn wound. The optimized concentration of gel-forming agent (Carbopol 940) was chosen based on best possible consistency and spreadability of the gel. The second-degree burn infliction was developed in the posterior region of rats followed by anesthesia. Afterward, the created wounds were further treated individually by both the gel formulation (1 application daily) for 14 days and observations were recorded. The nSSD gel showed better wound healing and a higher degree of tissue hyperplasia as compared with mSSD gel in rats. In vitro drug release study showed better drug release from nSSD gel (74.25 ± 3.331%) as compared with mSSD gel formulation (61.32 ± 2.112%) after 24 hours. The nSSD and mSSD topical gel-treated rats showed 95.63% and 78.75% wound healing after 14 days, while in the case of control group rats, 48.65% wound contraction was seen after 14 days. Furthermore, the histopathological study revealed that the nSSD gel was more efficient in controlling the wound infection and showed better wound healing as compared with mSSD gel formulation.

Lippia origanoides essential oil: an efficient and safe alternative to preserve food, cosmetic and pharmaceutical products.

AIMS: The aim of this work was to evaluate the efficacy and safety of Lippia origanoides essential oil as a preservative in industrial products. METHODS AND RESULTS: The composition, antimicrobial activity, mutagenic and toxic potential of L. origanoides were determined. Then, the effect of essential oil as a preservative in food, cosmetics and pharmaceutical products was evaluated. The essential oil of L. origanoides consisted mainly of oxygenated monoterpenes (38·13%); 26·28% corresponded to the compound carvacrol. At concentrations ranging from 0·312 to 1·25 µl ml-1 and in association with polysorbate 80, the essential oil of L. origanoides inhibited the growth of all the tested micro-organisms. The medium lethal dose in mice was 3·5 g kg-1 , which categorizes it as nontoxic according to the European Union criteria, and negative results in the Ames test indicated that this oil was not mutagenic. In combination with polysorbate 80, the essential oil exerted preservative action on orange juice, cosmetic and pharmaceutical compositions, especially in the case of aqueous-based products. CONCLUSIONS: Lippia origanoides essential oil is an effective and safe preservative for orange juice, pharmaceutical and cosmetic products. SIGNIFICANCE AND IMPACT OF THE STUDY: This study allowed for the complete understanding of the antimicrobial action and toxicological potential of L. origanoides essential oil. These results facilitate the development of a preservative system based on L. origanoides essential oil.

Validación prospectiva del proceso de fabricación de la doxiciclina DEF cápsulas / No disponible

Antecedentes y Objetivos. La doxiciclina es un antibiótico bacteriostático del grupo de las tetraciclinas, que actúa interfiriendo la síntesis proteica bacteriana. Se realiza el Desarrollo Farmacéutico del elaborado doxicilina DEF cápsulas, para el que se diseñan los métodos de control más adecuados en el nuevo proceso de fabricación que se considera, según los estudios galénicos realizados, como el más idóneo, proponiéndose su escalado industrial para una validación prospectiva. Se dispone en producción de dos encapsuladoras de la misma marca y modelo. Se analiza la variable encapsuladora por su posible influencia como factor crítico en el proceso. Lugar de realización. Centro Militar de Farmacia de la Defensa (Madrid). Material y métodos. El lote, mezcla del principio activo y los excipientes seleccionados, se divide en dos partes iguales para producir el elaborado en las dos encapsuladoras. Se realizan los ensayos de uniformidad de masa, uniformidad de contenido y de disolución. Se comparan las medias para datos apareados de estas tres variables. Resultados. Todos los sublotes fabricados cumplen con las especificaciones de calidad de las Farmacopeas. Existen diferencias significativas en la masa de las cápsulas y en el ensayo de disolución. Conclusión. El proceso se considera validado ya que las cápsulas de doxiciclina en los sublotes cumplen con los requerimientos de calidad descritos en las farmacopeas. Para disminuir las posibles diferencias intralotes, se rediseña el proceso de tal forma que se puedan utilizar las dos encapsuladoras

No disponible

The release of zinc ions from and cytocompatibility of two zinc oxide dressings.

OBJECTIVE: These in vitro studies examined the release of zinc ions from and the response of human dermal fibroblasts to two zinc oxide-medicated dressings: one with zinc oxide in an ointment base and one using polyvinylpyrrolidone (PVP), a hydrophilic polymer for the binding of zinc oxide particles. METHOD: Zinc release from the dressings in buffered-saline (pH 7.4) was studied through a high-pore-density membrane (pore size, 0.40 microm) in a two-compartment model at 37 degrees C for three hours. Cytocompatibility of the dressings and 500 micromol/l of zinc ions was assessed using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay after exposure to monolayers of confluent normal human dermal fibroblasts to the dressing extracts for four hours. RESULTS: The zinc release rate from PVP-bound zinc oxide was more than two-fold higher than from zinc oxide in the ointment. Extract of the zinc oxide ointment, containing 150 micromol/l solubilised zinc, elicited a cytotoxic reaction, while the zinc oxide-PVP extract, containing 410 micromol/l solubilised zinc, and 500 micromol/l zinc chloride were non-cytotoxic to the fibroblasts. CONCLUSION: Zinc release in a simulated wound milieu appears to be inhibited when zinc oxide is incorporated in a lipophilic vehicle. It is hypothesised that the ointment vehicle induced cytotoxicity rather then the solubilised zinc oxide. DECLARATION OF INTEREST: None.

In vitro-in vivo characterization of release modifying agents for parenteral sustained-release ketorolac formulation.

One of the prerequisites for a parenteral preparation is that the excipients incorporated are biocompatible and biodegradable. In the present study hydrophilic and hydrophobic excipients were investigated for developing an intramuscular sustained-release formulation of ketorolac. Kollidon 17 PF, Peceol (glyceryl monooleate), and castor oil were chosen as the potential release-retarding agents, each with a distinct mechanism of action. They were evaluated by in vitro drug-release profiles and in vivo pharmacodynamic and pharmacokinetic study in mice. Cumulative drug release was determined for standard and test formulations in modified Franz diffusion cell. Pharmacodynamic parameter, T = 70% response of peak analgesic response, was used to compare the performance of test formulations. Based on pharmacodynamic/pharmacokinetic correlation in the animal studies, Css(max) and Css(min) of 51.39 and 30.0 microg/mL, respectively, were determined and considered as performance markers for pharmacokinetic evaluation of test formulations. The study suggested that the sustained-release capability of glyceryl monooleate was maximum followed by that of castor oil and Kollidon 17 PF, when compared to conventional ketorolac tromethamine formulation. It was inferred that water soluble excipient, though, showed release retarding property in vitro but could not maintain it in the in vivo environment. Glyceryl monooloeate-based formulation produced the most favorable drug blood concentration vs. time profile.

Transdermal delivery of paracetamol for paediatric use: effects of vehicle formulations on the percutaneous penetration.

Paracetamol is a safe and effective analgesic and antipyretic agent, and is one of the most widely used medications for infants and children. The formulations currently available have been designed for oral and rectal administration. However, they are not practical in young patients with vomiting and diarrhoea, or in those who refuse to take the full dose. An alternative route of administration would be a significant contribution to the paediatric pharmacopoeia. The aim of this study was to develop a new transdermal system for optional therapeutic administration of paracetamol in infants and children. In-vivo studies were carried out in animals using a transdermal system of high-loaded, soluble paracetamol in a hydrogel patch, which was also tested in-vitro for 8 h. Although the beneficial contribution of glyceryl oleate to the transdermal penetration of paracetamol seemed to be significant in-vitro, it was shown to be insufficient in-vivo. To improve the penetration of the drug, 4% PEG-40 stearate and 10% ethanol were incorporated as absorption enhancers into the dermal patches. A few hours after application of the improved patches to rats, plasma drug concentrations were elevated to levels comparable with those obtained after oral and subcutaneous administration of a high dose of paracetamol. Since plasma drug concentrations did not reach a constant steady state (as a peak or plateau) during the short-term animal experiments, longer pharmacokinetic studies in conscious animals are necessary.

The influence of platelet additive solutions on cytokine levels and complement activation in platelet concentrates during storage.

BACKGROUND AND OBJECTIVES: The accumulation of platelet-derived cytokines in platelet concentrates (PC) during storage may contribute towards non-haemolytic transfusion reactions (NHTR). We investigated the effect of platelet storage medium on platelet activation, complement activation and cytokine levels in leucocyte-reduced PC. MATERIALS AND METHODS: Hyperconcentrated platelets (3000-6000 x 109/l) were collected by apheresis and diluted in 100% plasma, 70% PASIII, or 70% or 80% PASIII supplemented with magnesium and potassium (PAS IIIM). RESULTS: Levels of transforming growth factor-beta (TGF-beta) and regulated on activation, normal, T-cell expressed, and secreted (RANTES) increased during storage, as did the expression of P-selectin (CD62P), and were highest in PC stored in PASIII. In PC stored in PASIIIM, however, levels of TGF-beta and RANTES were not significantly different from PC stored in plasma. Levels of CD62P expression, however, remained higher in PASIIIM PC than in those stored in plasma by day 5, but were lower than PC stored in PASIII. C3a des arg levels increased during storage in all media with the exception of PASIII and, on day 7, were higher in PC stored in plasma compared to PC stored in the other media. CONCLUSIONS: Our results indicate that replacing plasma in PC with unmodified PASIII for storage results in higher levels of platelet-derived cytokines in PC. Furthermore, it appears that the nature of the medium used for storage of PC has a significant impact on platelet activation and cytokine levels of the PC. These implications should be taken into account when considering replacement of plasma with PAS.

[The antimicrobial activity of a new wound-healing compound ointment]. / Antimikrobnaia aktivnost' novoi kompozitsii ranozazhivliaiushchei mazi.

Drug composition containing polyethyleneoxide PEO-400 and PEO-1500 (8:2), antimicrobe agent-chloramphenical as well as new antiinflammatory mean of plant origin EOL in concentration of 5% has been created. Introduction of EOL to the composition of the drug under elaboration permitted decreasing chloramphenicol concentration 2-4 times as compared to concentrations used in contemporary ointments. This has lowered toxic and allergenic properties of the drug suggested for healing the infected wounds.

[Effects of bio-mineral food additive on health].

Spartina alterniflora, one kind of bio-mineral food additive and special nutrient liquid, rich in bioactive materials, was extracted from a marsh plant grown in beach. It can enhance immune function of animals and human bodies, increase the tolerance to hypoxia in rats, prolong life span of fruit flies, and increase activity of human serum superoxide dismutase.

The influence on the dermal cellular infiltrate of topical steroid applications and vehicles in guinea pig skin: normal skin, allergic and toxic reactions.

The mechanisms of the anti-inflammatory effects of corticosteroids are uncertain but could be explained by an influence on infiltrating leukocytes. Our method for the qualitative and quantitative investigation of the dermal cellular infiltrate makes it possible to study the effects of topically applied corticosteroid preparations and vehicles on the infiltrating leukocytes of normal skin, allergic and toxic reactions in guinea pig skin. Ointment and cream vehicles as well as corticosteroid cream and ointment preparations often caused erythema and increased mononuclear infiltrate after only short periods of application (24-72 h). The strongest steroid ointment gave the most marked macroscopic response and propylene glycol preparations the most marked cellular response. In both toxic and allergic reactions, application of steroid preparations after the provocation gave no beneficial result either macroscopically or microscopically. Macroscopic scores were worsened by cream and ointment preparations. Although steroid solutions had no beneficial effect, they caused no detrimental effect. The guinea pig seems to be extremely sensitive to irritants and has not proved to be a suitable model for this approach to the study of the efficacy of topically applied steroids.

Histological changes in rabbits after application of medicaments and cosmetic bases. II.

A further study of the topical effects of certain pharmaceutical and cosmetic bases on rabbit skin is reported. Cetyl alcohol, myristic acid, castor oil and sorbitol were applied in fixed doses daily for 30 days and their irritant activity was assessed. The macroscopic and microscopic changes were on the whole minimal. Castor oil alone produced some macroscopic alterations in the form of slight erythema and edema, and microscopic changes consisting of acanthosis, disorganization of the basal layer and slight infiltration of the dermis.

[Bioavailability of tetracycline hydrochloride capsules (an in vivo study)]. / Biodostupnost' kapsul tetratsiklina gidrokhlorida (issledovanie in vivo).

Blood absorption of tetracycline hydrochloride of various dispersity levels from capsules containing tetracycline alone or in combination with additives, such as magnesium carbonate and calcium salts was studied on humans. It was found that higher dispersity levels of tetracycline hydrochloride powder in capsules was not accompanied by increased blood absorption of the antibiotic. Addition of magnesium carbonate and calcium salts to the antibiotic in the process of capsulation markedly retarded the blood absorption. Clear correlation between the antibiotic dissolution rate in vitro and intensity of its blood absorption in volunteers was shown.

[Study of the pharmacological properties and safety of a solution of levomycetin in hexamethylene tetramine for intravenous administration]. / Izuchenie farmakologicheskikh svoistv i bezvrednosti rastvora levomitsetina v geksametilentetramine dlia vnutrivennogo vvedeniia

Pharmacological properties of 2 per cent levomycetin solution in 40 percent hexamethylentetramine solution, as a new pharmaceutical form of levomycetin for intravenous administration prepared at drug-stores were studied. The maximum tolerating doses of the drug for mice, rabbits, and dogs were 26-47 times higher than the therapeutic ones with respect to the content of levomycetin and hexamethylentetramine. No increase in the toxicity of levomycetin and hexamethylentetramine in the preparation was observed. The drug in the doses 16 times higher than the therapeutic ones by the content of levomycetin did not almost change the arterial pressure and the drug in the doses 3.7 times higher than the therapeutic ones did not affect the blood coagulation either in acute experiments, or on its prolong intravenous infusion. Repeated administrations of the drug to rats and rabbits for 15-18 days in doses 3.7-4.8 times higher than the therapeutic ones by the content of levomycetin were innocuous for the animals. Absorption, circulation in the blood, distribution in the tissues and excretion with the urine of levomycetin used in the above pharmaceutical form did not differ from circulation of the antibiotic on its intravenous and oral administration. The drug is recommended for use in medical practice.