M. A. Ruiz

Multilamellar liposomes of triamcinolone acetonide: preparation, stability, and characterization

The aim of this study was to assess and characterize the stability of multilamellar liposomes as a delivery vehicle for triamcinolone acetonide. A standardized preparation method for a liposomal delivery vehicle was developed, after varying composition and storage conditions, and assessing encapsulation efficiency and loss of active principle. The assessment of temperature as a factor in formula stability during storage showed that stability improved under refrigeration (4–6°C) (less early diffusion of active principle through the liposomal wall), in comparison with samples stored at room temperature. To improve stability, cholesterol was added to some formulae, which although resulting in a decrease in average encapsulation efficiency, mitigated subsequent losses of retained active principle (formulae 4, 5, and 6), in comparison with those without cholesterol (formulae 1, 2, and 3). This was evident both under refrigerated and room-temperature conditions. Finally, after testing the effects of adding an antioxidant and/or preservative to the formulae, a liposomal design was achieved with acceptable stability, vesicle dimensions, and encapsulation efficiency.

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.

Determination of the stability of omeprazole by means of differential scanning calorimetry

Differential scanning calorimetry was used to study the stability of omeprazole in two forms: granules and powder. The drug was subjected to light, elevated temperature (40 and 60°C) and different pH values. The greatest alterations in stability were caused by pH, followed by light.

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.

Measurement of dynamic surface tension to determine critical micellar concentration in lipophilic silicone surfactants

Silicone surfactants are becoming increasingly important in the pharmaceutical and cosmetic industry, because of their versatility, low cost, and technological advantages. The present study was designed to measure the critical micellar concentration of three non-ionic silicone surfactants, one water-soluble and two lipid-soluble. We measured surface tension with a technique based on drop geometry. Solubility and dispersibility in water were tested in the two lipophilic surfactants with visible and UV light spectrophotometry. The data obtained with all techniques showed a characteristic behavior of lipophilic silicone surfactants, which did not entirely conform to the definition of critical micellar concentration.

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).

Effect of cellulosic polymer on the release of salicylates in topical formulations

In this work, the effect of cellulosic polymer and chemical structure of salicylic acid and its various esters on their release has been analysed. The release of different drugs in distinct types of vehicles, cetyl excipient, polyethylene glycol and Carbopol gel was also studied.

Formation of ondansetron polymorphs.

We used differential scanning calorimetry, infrared spectrophotometry and 1H nuclear magnetic resonance imaging to search for polymorphs of ondansetron. Samples were tested under different conditions of temperature, pulverization and pH, and in different solvents. The factors identified as able to cause the formation of polymorphs were heating to different temperatures for different times, and the use of ethanol and methanol as solvents.

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.

Spectrophotometric and chromatographic determination of omeprazole in pharmaceutical formulations.

The purpose of this study was to determine the stability of the pH sensitive drug, omeprazole, within different solid oral pharmaceutical formulations and to determine whether the addition of antacid and surfactant agents, at varying concentrations, influenced drug stability and release. Spectrophotometric and chromatographic techniques were used for evaluation purposes, giving good results concerning linearity, precision and specificity within the range of concentrations used in this study. However, the results show that the degradation products of omeprazole interfere with spectrophotometric evaluation, making this technique insufficiently selective for omeprazole. On the other hand, liquid chromotography proved to be more sensitive, accurate and precise. Additionally, in an attempt to improve the administration form of the drug, an extemporaneous suspension was designed, which after evaluation proved to be a satisfactory administration vehicle. The best formulation of omeprazole studied is: omeprazole: 0.5%; corn starch 34.2%; aluminum hydroxide 26%; magnesium hydroxide 13%; simple syrup 24.8%; SDS 1%.