María Encarnación Morales

Preparation, Rheological Study, and Characterization of an Organogel as a System for Transdermal Release of Active Principles

The use of formulations containing Pluronic® gel as a vehicle and permeabilizing agent for transdermal preparations has increased in recent years. We prepared and compared two transdermal formulations for drug administration as an alternative to oral or parenteral administration. In formulations containing Pluronic® F127 gel or pluronic lecithin organogel (PLO), rheological, structural (transmission electron microscopy) and physicochemical characteristics were studied under different conditions of composition, temperature, and time from 24 hr to 3 months after preparation. Rheological studies at 20–25°C and at 4°C to study the influence of refrigeration on viscosity and pH showed that both formulas were thermoreversible. Unilamellar vesicles smaller than 1 μm in diameter were seen in the PLO formulation on TEM observation. The characteristics of these excipients may facilitate the application and may avoid the gastrointestinal tract and the first-pass effect.

Preparation, characterization, and in vitro release of new transdermal methimazole as alternative to oral delivery.

Our objective has been the development and study of the stability of transdermal methimazole formulae as alternative to oral administration. Preparation of F-127 and PLO Pluronic gel (Pluronic lecitin organogel) are described, as well as their characteristics from transmission electron microscopy. The possible structural and rheological changes to both transdermal forms were studied in terms of composition, temperature and time. The trial period was from 24 hr to 3 months after preparation. Furthermore, identical tests were carried out on formulae conserved for 1 year after production to check their integrity. Studies of release in vitro were carried out showing that the selected excipients do not pose an obstacle to the cession of methimazole, even though the PLO samples were made more slowly.

Design, development and characterization of buccal bioadhesive films of Doxepin for treatment of odontalgia.

Abstract Tricyclic antidepressants, as doxepin hydrochloride (DH), may have analgesic local effect due to its biochemical mechanism of action. Delivery of DH directly to the oral cavity could be an interesting alternative for toothache due to its analgesic local effect. One problem associated with the mucosal administration routes is the short residence time of the dosage form on the mucosal membranes. In this sense, we have developed new doxepin mucoadhesive films able of reducing pain and increasing the effectiveness of treatment. For this purpose, we tested three different polymers: chitosan, sodium hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (SCMC) in film elaboration. The results obtained show that all films are hydrophilic matrices that absorb water when placed in an aqueous media. All the films hydrated very quickly, reaching high percentage of swelling after just few minutes (5 min for SCMC, 2 min for HPMC and 30 min for chitosan). Moreover, the SCMC and HPMC films were dissolved whereas chitosan was not dissolved. Dissolution also leads to viscous liquids with a higher retention time over mucosal surfaces what may lead to adhesive interactions. In vitro permeation studies showed that for all the formulations studied, SCMC (19.91%), HPMC (69.5%) and chitosan (24.17%), the percentage of drug permeated increased compared to the drug solution (8.26%). Specifically the HPMC film presents greater amounts of doxepin permeated (49.27 ± 4.47 µg/cm2).

Development of oral suspensions of microparticles of ethylcellulose with tramadol

Background: Although tramadol has less analgesic power than morphine, it presents fewer side effects and consequently is currently considered as a drug of choice in the treatment of chronic pain. The objective of this work was to obtain a sustained-release liquid preparation for oral administration, using pseudolatex of ethylcellulose as a delivery vehicle of the active principle. Methods: Once an appropriate microencapsulation had been achieved, different formulations with different viscosing agents were designed and subsequently subjected to in vitro release studies, using Franz-type diffusion cells. Results: The pseudolatex with tramadol showed an encapsulation efficiency of 82% but was found to be dependent on the quantity of the drug. The images obtained through scanning electron microscopy showed sphere-shaped particles with a porous surface and diameter sizes of 3.5 and 5.5 μm. Infrared spectrophotometry and calorimetric analysis revealed the formation of a drug–polymer complex. Of the formulations proposed, that with xanthan gum released 46% of the drug, whereas Carbopol®, sodium carboxymethylcellulose, and Avicel® gave 50% and 55%, respectively. All followed a release kinetic of cube root, with the release mechanism of the active principle occurring through anomalous transport. Conclusions: In accordance with the studies performed, we can confirm a liquid pharmaceutical preparation for oral use, capable of providing a sustained release of tramadol.

A novel double-layer mucoadhesive tablet containing probiotic strain for vaginal administration: Design, development and technological evaluation

ABSTRACT Vulvovaginal candidosis caused by Candida spp. is the most prevalent vaginal infection in Europe and the second one in EE.UU, so it has become a major female concern. Probiotics bacteria have been proposed as an alternative treatment with the aim of avoiding the adverse effects associated with conventional therapies including antibiotics and other aggressive drugs for the vaginal mucosa and microbiota. The purpose of this work was to design and develop a novel vaginal tablet that contained Lactobacillus spp. bacteria as a treatment against vulvovaginal infections. A total of 21 two‐layers vaginal tablets, which contained different polymeric ratios, were proposed. However, formulation F4 (20 mg Na‐CMC; 50 mg Carbopol® 934; 20 mg chitosan) was selected as optimal according to its swelling index and dissolution/erosion capability. F4 tablets showed suitable technological properties for vaginal administration as well as mucoadhesion time (24.36 ± 0.88 h) and force (0.0941 N). Disintegration assay in simulated vaginal fluid (SVF, pH 5.5) showed that effervescent layer disappeared in 27.48 ± 0.05 s whilst matrix layer was totally gelled in 1 h. Two different release profiles were achieved; on the one hand, a promptly release due to the dissolution of both effervescent layer and matrix layers surface (1.10 × 108 CFU/g), on the second hand, a prolonged released of the remaining bacteria until 24 h (5.48 × 107 CFU/g). For stability and storage study, it was found that bacteria viability was constant until 90 days in both ways of storage, in a desiccator and at room temperature, with a final dosage of 108 CFU/g which was considered appropriate for vaginal therapy (108–1010 CFU/g). &NA; Graphical abstract Figure. No Caption available.

Microorganismos probióticos y salud.

Objetivo: Mostrar los beneficios de los microorganismos probioticos sobre la salud y su aceptacion por parte del consumidor, asi como hacer una recopilacion de todos los productos probioticos disponibles en el mercado farmaceutico. Material y metodos: Se realizo un estudio del mercado farmaceutico en relacion a las formas farmaceuticas con microorganismos probioticos existentes y su evolucion en los ultimos anos. La clasificacion de todos los productos probioticos se llevo a cabo en funcion de la forma farmaceutica en la que se presentan;cada producto ira acompanado de la dosis de microorganismos probioticos que contiene, expresada como Unidades Formadoras de Colonias (UFC). Resultados: Es cada vez mayor el numero de cepas probioticas aisladas y los beneficios mostrados sobre la salud del hombre. Encontramos gran diversidad de productos probioticos disponibles en oficinas de farmacia como consecuencia de una demanda cada vez mayor por parte del consumidor; no obstante, cabe resaltar el hecho de que muchos de ellos carecen en envase de informacion necesaria, por ejemplo, la dosis contenida. Conclusiones: El interes por parte de la industria farmaceutica en lazar nuevas formas farmaceuticas contenidas en microorganismos probioticos sera cada vez mayor e ira ligado a la necesidad de una reglamentacion especifica para estos productos. Muchos de ellos no contienen la dosis minima requerida para obtener un efecto beneficioso en la salud lo que supone una publicidad enganosa para el consumidor, por tanto, deberian ser retirados del mercado, publicitando unicamente aquellos que contengan una dosis terapeutica y cuyos efectos esten avalados por diferentes ensayos clinicos.

Evaluation of Tablets Containing a Probiotic Strain for an Oral Administration

The scientific concept of probiotics has been widely accepted throughout the last decades; consequently, its industrial production and commercialization have been increased. This is only the beginning since a recent global probiotic market analysis estimated an annual growth, boosted mainly by a rising request from the Asian and European consumer in the next 5 years. So the pharmaceutical industry needs to develop new dosage forms containing probiotic microorganisms in order to offer consumers a variety of products. Different kinds of matrix tablets with Lactobacillus coryniformis CECT 5711 were designed to protect this strain from the technological process and harsh gastrointestinal conditions up until their arrival in the gut, as well as environmental conditions during their storage. With this aim, various retarding polymers were combined so as to get controlled release tablets. All formulations were evaluated in terms of technological processability, bacterial viability and stability. Finally, an optimal formulation with Methocel K-15 M EP, Eudragit L-100 and alginate sodium, which contain Lactobacillus coryniformis CECT 5711, was selected due to the fact that it assured an excellent survival of the microorganisms after their exposition to all conditions mentioned above, besides it will be able to improve human’s health.

Microencapsulation of probiotic cells: applications in nutraceutic and food industry

Manipulation of gut microbiota with probiotics has gained increasing interest, since they have demonstrated beneficial effects in the maintenance and promotion of health. Different approaches that increase the resistance of these sensitive microorganisms against adverse conditions have been studied. The most recent studies indicate that microencapsulation is one of the most efficient methods, and it has been under especial consideration and research. In this sense, some benefits of cells microencapsulation include the protection from bacteriophages and detrimental factors, thus increasing survival during freezing, freeze-drying, and storage and allowing researchers to obtain a probiotic powder that is easy to use and to incorporate into food or pharmaceutical matrices. Therefore, the aim of the present chapter is to describe the techniques for probiotics microencapsulation, the compounds used in the microencapsulation process, as well as applications in the food industry.