PREPARATION OF DRUGS

Author: ARIZA OSORIO AIDA M..
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: The aim of the doctoral thesis is the development of transdermal systems in which the transfer of the active ingredient is going to be controlled by a synthetic membrane developed with colodión and various proporcionesde.una substance aplastificante. TO change the ratio of piastificante can be achieved. The speed of transfer of the active ingredient to be transñera their means, vary equally fomla. That is, depending on the amount of plasticizer can be obtained velocidades.de different assignment for transdermal systems developed in which the transfer of the active ingredient. Va. To be controlled by a membrane, it is necessary to first obtain a series of synthetic membranes composed all for colodión as inert carrier and different proportions. A substance plastiñcante (castor oil), which is what we are going to serve to control the speed of transfer of the active formulado.en the transdermal system. With these components are two types de.membranas synthetic elaboration: about without the active and others in its structure containing the active ingredient. The technical development will be the same for both, the only difference would be whether or not the prindpio active. It was chosen as the tracer substance acid Salicilico because it is a principle activo.ampliamente used in dermatology and is easy to assess spectrum photometry. Studies assignment will be carried out with each and every one of the membranes prepared, in order to choose the most suitable for transdermal systems to be developed below. The systems transdermal constaIán a reservoir containing the active ingredient formulated as emulsion O / AY of the synthetic membrane, selected from among those prepared earlier, which will serve to control the amount and speed of transfer of fárnaco. In order to optimize systems transdermal well elaboIados will carry out studies in vitro transfer of active ingredient contained in the same samples using human skin.

Author: RINCÓN ALARCÓN ADRIANA CAROLINA.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: The design of new systems therapeutic intraocular administration has become a major concern in recent years, become increasingly pathologies affecting the segment back of the eye and vision that compromise in a high percentage of patients. It is important in this area, the introduction of new biomaterials that, maintaining its biocompatibility, are able to incorporate and properly assign the active substance. The aim of this study was the evaluation of poly (Valina-Prolina-Alanina-Valina-Glicina) [VPAVG], polymer belonging to a family of novel materials bioelásticos derived from elastin, as a trainer assignment controlled systems for the channel Intraocular. We obtained this polymer aggregates of variable size depending on the concentration of poly (VPAVG) present in the formulation. The rate obtained for the encapsulation phosphate dexamentasona decreases to half that increases the concentration of polymer. The initial assignment of the drug was superior to 64% and from the third day of trial, this process was slowed cediéndose, after 42 days, between 94 and 97% of the amount of active substance incorporated. The evaluation of its tolerance "in vitro", it was observed as cellular respiration were not significantly affected by the concentration of the polymer. By subcutaneously, the particles of this biomaterial showed an excellent tolerance to not induce inflammation in the rat paw. However, when it conducted its administration intravitrea there was a detachment traccional of the retina, which were not suitable to be used in this way. Finally, we evaluated the impact of gamma radiation on the biomaterial and formulations, determining susceptibility of both this type of radiation as a method of sterilization, which was raised resorted to other methods to ensure their sterility end.

Author: RAMÍREZ SALCEDO LORETO.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA DE U.C.M..

Summary: Retinitis cytomegalovirus (CMV) is the opportunistic eye infection that appears more frequently in patients suffering from acquired immune deficiency syndrome (AIDS). Without adequate treatment, necrosis of tissues eye becomes progressively, with the risk of a total loss of sight in a high percentage of subjects. Ganciclovir is one of the most commonly used drugs in the treatment of CMV retinitis, and is used intravenously, orally and itranocular. The intravenous treatment is tedious and is associated with significant side effects, a fact which requires discontinuation of therapy. For oral administration used a prodrug of ganciclovir (Valganciclovir), with levels that are effective. However, it has been shown that it is more effective local treatment of infection Check the injections intravítreas of ganciclovir delayed, in an effective way, the progression of the disease. However, the short half-life of ganciclovir requires that the frequency of administration of injections is twice a week. Although this treatment is effective, injections intravítreas are poorly tolerated are associated with side effects. Currently, there is an implant on the market of non-biodegradable ganciclovir to attain adequate concentrations in the vitreous during 5-8 months. However, this non-biodegradable implant has certain disadvantages because it is expensive and its size also makes it necessary to require two surgical procedures. The biodegradable systems management drugs have the advantage of disappearing from the place of action once exercised the desired effect. In this report have developed biodegradable microspheres of ganciclovir, of various sizes, from two polymers derived acid poli-láctico-co-glicólico (viscosity inherent 0.2 and 0.4 dl / g) and has been used as additive controller, oil flurosilicona and vitamin E. Fractions granulometric tested have been 212-300 um, 300-500 um and 500-1000 um. We have selected the design prepared from polymer viscosity inherent 0.4 dl / g, using vitamin E as an additive in size between 212-500 um. These biodegradable devices can be managed as a conventional intraocular injection and thus avoid surgery. Sterilization end of the particles was carried out by gamma radiation, using a dose of 25 kGy. The terms of the sterilization process employed to do this work, have helped keep the properties of the selected formulation.

Author: SALVADOR VELASCO ANGEL.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: Research work on the use of animal medicine used by albéitares and herradores number of RealCaballeriza after marisacles number, for the treatment and prevention of diseases in cattle from the Royal Caballeriza during the reign of Charles IV, Ferdinand VII and Elizabeth II. Take this prolix bureaucracy accounts monthly expenses to learn, in addition to therapeutic use, acts professionals and steps taken hygienic. We studied all pesonas related to the prescription and application of medicine during our study period, either number marshal, marshal supernumerary, herrador road aid herrardor, mancebo medicine or any other intermediate position of the ladder. The dating work allows us to introduce us to the time of commencement of the School of Veterinary Medicine, Madrid, Spain first and the subsequent takeover of the Royal Court of Protoalbeitarato by the College, which means the end of an old profession, the Albeitería and the final development of veterinary. We provide a vision to complement these developments take place from the Royal Caballeriza, closely linked to both institutions.

Author: MORENO CEREZO JESÚS M..
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: The formation of inclusion complexes by intermolecular interaction of a drug with another substance, causing significant changes in physico-chemical properties and biofarmacéuticas it. It has recently become very important use of inclusion complexes with cyclodextrins due to its various uses and its great potential availability on the market. Among the most important actions that exercise highlights an increase in the solubility and dissolution rate of slightly soluble drugs, resulting in an improvement of the bioavailability and increased stability principiosactivos. The Indomethacin is an active ingredient with anti-inflammatory activity and non esteroídico (NSAIDs) for its inhibitory capacity of cyclooxygenase, trainer of prostaglandin. The main constraint to its development is the low water solubility that show, which hinders the process of dissolution of the drug in gastrointestinal fluids and determines its toxic effects and treatment as their ultimate impact depends on its ability to dissolve and transferred through the biological membranes. The solubilization of certain drugs is one of the most important challenges for the farmacotecnia a formulation galénica that can be solved in this important part problema.La beta-ciclodextrinaes able to include within its cavity different molecules and form inclusion complexes. The unique feature of the complex is the most solubility, getting in the case of drugs from the group of NSAIDs rapid and prolonged effect analgesic - antiinflammatory drugs, without resorting to dispersible forms or forms retard. Within the group of Tetracyclines and specifically as hydrochloride, wide range of oral antimicrobial activity and bactericidal action, it is worth noting the significant toxicity presenting its degradation products, especially epímero 4-epi-anhidro-tetraciclina ( 4 EATe). The very Pharmacopoeia of the United States USP sets a maximum value of 4EATC no more than 3.0% of the dose found in solid forms. The content of active ingredient in several formulations may decrease over time due to degradation processes such as hydrolysis, oxidation, etc.. Occurring during storage. They can also degrade by heat or light, or suffer reactions with other components of the formulation. Many drugs can be stabilized compared to their degradation by the inclusion with cyclodextrins. The possibility of including all or part of the molecule's active Tetraciclina hydrochloride inside the cavity of cyclodextrin, and specifically in our study with hydroxypropyl derived from beta-ciclodextrina, is the strategy that we used technology to enhance stability the drug formulations. There has been the development of pharmaceutics study preformulación ranging from the combination of Tetraciclina hydrochloride with the excipients selected, depending on the formulations alleged evils until a study of accelerated stability; always based on the bibliographic information gathered and They provide us with our own experimental results.

Author: JO CARDOSO ENRIQUE.
Year: 2004.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE FARMACIA.

Summary: The experimental work has helped establish developed a model of cubic splines adjustment in determining temperatures estécticas from data obtained through technical term conductivity. It has established a simplified thermal characterization which enables fingerprint thermal (HDT) of products liotilizar. It has developed a product for the application of thermal perimeters in the parameterization of out of liosilización three thermal known: vancomicire acl 500mg. Aciclovir 250 mg and Pontamidine diesetioneto 300 mg. In the first seha achieved elminar appearance stratified dela pill has been reduced and the process in 19 hours in the second reduced respect to a business cycle in 26 hours, the third time has been reduced total process in 32 hours.

Author: POSE VILARNOVO BEATRIZ.
Year: 2005.
University: SANTIAGO DE COMPOSTELA [www.usc.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: This paper seeks to combine the potential of cyclodextrins, as promoters of the solubility of drugs, with the ability of hydrophilic polymer to control the transfer of the active ingredient, when it is made into tablets matrix. Prior has studied the effect of polymer selected, the hidroxipropilmetilcelulosa, on the effectiveness of complexation of cyclodextrins. The study has been raised with the aim of developing tablet matrix, hidroxipropilmetilcelulosa and cyclodextrins of two drugs from different physico-chemical characteristics; sulfametizol and diclofenac sodium ion and not the sparingly soluble and water-soluble ionic first and the second. It has analyzed the effect of complexation on the solubility of both drugs and the influence of interactions ciclodextrina-polímero hydrophilic on the characteristic of cesíón active substance from matrix tablets. The study was conducted in the following stages: A.-Preparación and characterization of inclusion complexes of both drugs with cyclodextrins. We analyzed the influence of cyclodextrins (beta, and hidroxipropil-beta-ciclodextrinas) on the solubility of the active ingredients elected. B. Analysis of the effects of hidroxipropilmetilcelulosa in the process of complexation. C. Consideration of the influence of cyclodextrins on the assignment of two active ingredients from gels and tablets matrix hidroxipropilmetilcelulosa. The use of cyclodextrins can be a useful tool for modulating the release of drugs from matrix tablets. The influence of these additives could be related to the molecular size of the drug and the hidrofília of cyclodextrin. The results are shown in the following publications. 1. B. Pose Vilarnovo, L. Santana Penín, M. Echezarreta Lopez, Ms Marcos Perez, JL Vila and JJ Jato Torres Labandeira. Interaction of diclofenac sodium with beta and hydroxipropil- beta-cycfodextrin in solution. STP Pharma Sciences 9 (3) 231-236,1999. 2. B. Pose-Vilarnovo, 1.Perdomo-López, M. Echezarreta-López, P. Schroth-Pardo, E. Estrada and J. J. Torres-Labandeira. Improvement of water solubility of sulfamethizole through its complexation with - and hydroxypropyl- -cyclodextrin. Characterization of the interaction in solution and in solid state. European Journal of Pharmaceutical Sciences, 13, 325-331, 2001. 3. B. Pose-Vilarnovo, C. Rodríguez-Tenreiro-Sánchez, MB Marcos Perez and J. J. Torres-Labandeira. Sulphamethizole-cyclodextrin- ydroxypropylmethylcellulose mutticomponent complexes. Journal of Thermal Analysis and Calorimetry, 68, 657-667, 2002. 4. B. Pose-Vilarnovo, C. Rodríguez-Tenreiro-Sánchez, N. Diéguez Moure, JL Vila-Jato and JJ Torres-Labandeira. Effect of hydroxypropylmethylcellulose on the complexation of diclofenac with cyclodextrins. Journal of Thermal Analysis and Calorimetry, 73, 661-670, 2003 5. B. Pose-Vilarnovo, C. Rodríguez-Tenreiro, JF Rosa dos Santos, J. Vázquez-Doval, A. Concheiro, C. Álvarez-Lorenzo and JJ Torres-Labandeira. Modulatingdrug releasewith cyclodextrinsin hydroxypropyfmethylcellolosegels and tablets. Joumal of ontronedRelease, 94351-363, 2004.

Author: ROSAS PÉREZ JAVIER EDUARDO.
Year: 2005.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: SPf66 is the first chemically synthesized vaccine that induces a partially protective response against malaria. The vaccine, SPf66 is weakly immunogenic when given adsorbed on aluminum hydroxide gel as an adjunct to poor and moderate effectiveness in humans. In order to improve the immunogenicity of this vaccine is developing a system for administration, based on its microencapsulation microspheres produced with biodegradable polymer derived poli-D, L-láctico-co-glicólico (PLGA). The microencapsulation of immunogen SPf66 was done by the technique of forming a double emulsion with subsequent evaporation / solvent extraction (w / o / w). The formulations were properly characterized in all its properties biofarmacéuticas and subsequently evaluated its ability to induce an appropriate immune response in two animal models, mice BALB / c and non-human primates gender Aotus. The results in vitro and in vivo showed that there was no effect of the microencapsulation process in the integrity of the antigen, and that these formulations, in both animal models employees, filed the ability to induce a better immune response than the one obtained when used hydroxide aluminum as an adjunct and comparable to that obtained when used in Freund's adjuvant. Additionally, it was determined in a preliminary manner that there is a considerable effect on the properties bioframacéuticas this system microparticular or on the biological activity of immunogen SPf66, after being subjected to a process of gamma irradiation, in order to evaluate this process as the final sterilization method for these systems for the delivery of antigens synthesized chemically as SPf66, in a single dose.

Author: Rodríguez Pérez Ana Isabel.
Year: 2006.
University: SANTIAGO DE COMPOSTELA [www.usc.es].
Place of defense: Facultad de Farmacia.
Place of preparation: Facultad de Farmacia.

Summary: The effect of different cyclodextrins (CDs) on the solubility, dissolution rate and the antifungal activity of nitrate sertaconazol in aqueous medium, in the absence and presence of hidroxipropilmetilcelulosa, HPMC or a copolymer tribloque anfifílico, pluronic F127 ( PF127). Microbiological studies performed with Candida albicans showed that the increase in solubility leads to the drug complexation with cyclodextrins in a very remarkable improvement its antifungal activity. The study in detail the process of complexation of sertaconazol was carried out by molecular modeling techniques, which provided information about the most stable conformation, and resorting to conventional experimental techniques based on the determination of the solubility (media and different pH by applying various heat treatments) and microcalorimetría isothermal. The results obtained by this technique revealed that estequiometría of inclusion complexes is highly dependent on the pH, and at pH 1.2 dominates the complex drug: CD 1:1, increasing the likelihood of forming complex 1:2 as increasing the pH. It was also observed that there may be different complexes with the same estequiometría by penetration of various chemical groups of the drug in the cavity of the CD. Incorporating micelles PF127 to dissolutions CD low concentration resulted in an additive effect on the solubility, but if it increases the concentration of CDs is manifested antagonistic effect due to the formation of complex cyclodextrin: unímero of PF127. The complex in solid obtained by lyophilization or malaxado showed a profile of dissolved faster than the corresponding physical mixtures. In addition, the gelling ability of PF127 permits regulate the speed of the process.