58 research outputs found
Thermal analysis of systems containing theophylline and three types of Compritol
No full textThe use of fluid-bed or spray-drying processing in the development and production of solid dosage forms is increasing. These processes are traditionally used for granulation and the drying and coating of powders, granules, tablets, beads. Generally speaking, the coating material is dissolved in a solvent (water or organic) prior to spraying. During and after coating the solvent must be evaporated. The use of solvents nowadays is under constraint due to the problems of trace levels, while recovering a solvent often proves expensive. Moreover also long evaporation time of the solvent (especially water) could be a problem. In order to avoid such problems and to reduce costs, it is appealing to use meltable materials, such as waxes or derivatives or other different low-melting lipid materials – as coating agents.
The aim of the present study was to analyse the ability of different types of Compritol, namely Compritol 888 ATO (glyceryl di-behenate), Compritol E ATO (mixture of mono-, di- e tri-glycerides of behenic acid: mp 67-80°C) and Compritol HD5 ATO (mixture of glyceril di-behenate and PEG -mp. 60-67°C) to sustain the release of theophylline, used as tracer model drugs incorporated into a solid dispersion prepared by the melting method using the three lipid materials.
Formulations with drug:Compritol 10, 20 and 30 % w/w were evaluated: physical mixtures were heat treated at 80°C for 10 min to prepare the solid dispersions. The material thus obtained was maintained at -20° for 2 days and then milled and sieved.
Samples of each formulation were analyzed by DSC and HSM, revealing the different solvent ability of the molten phase of each Compritol. In fact at HSM, after the melting of the carrier, undissolved theophylline particles are clearly evident at all the compositions examined that demonstrated to dissolve into the molten carrier at increasing temperature. This event was not documented by DSC thermograms that therefore did not offer important information. HSM technique revealed also suitable to examine the effects of aging. After 6 months comparison of similar situations (composition, temperature, and nature of the carrier) revealed the presence of a larger amount of crystallized material. Increased particle amount was due to crystallization of previously dissolved drug, during the preparation of the solid dispersion that, in the presence of the solid carrier was only delayed. This fact was also confirmed by dissolution profiles: a control of the release was obtained only at the lowest concentration, while at higher concentrations no difference could be observed with respect to pure theophylline: this was hypothesized as due to better coating of the drug particles by the lipid carrier, suggesting at the same time that the concentration range, useful to obtain a control of the release of theophylline, is quite restricted.
Better results, in terms of control of the release, were obtained if the molten phase was spray-congealed using an ultrasound assisted device. In this case the process allowed obtaining spherically shaped microparticles: SEM and HSM observation indicated that single theophylline particles were coated by the lipid material that could slow down dissolution of the drug with respect to pure drug. On the contrary in the final dispersion, after solidification, the milling could have acted along fracture lines that made free the drug particle surface, hindering any control to the release by the lipid material
Development of microparticles for oral administration of the non-conventional radical scavenger IAC and testing in an inflammatory rat model.
No full textDevelopment of microparticles for oral administration of the non-conventional radical scavenger
IAC and testing in an inflammatory rat model
1)Cirillo S.. 2)Paolini M.. 3)Vivarelli F.. 4)Passerini N.. 5)Albertini B.. 6)Di sabatino M. 7)Corace G.. 8)Luppi B..
9)Canistro D..
University of Bologna
The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) is an innovative nonconventional
radical scavenger used with success in several disease models, such as inflammation,
neurological disorders, hepatitis and diabetes. To date, the main limit for the drug use is
represented by the intraperitoneal (i.p.) route of administration used in the pharmacological
treatments. In order to develop a delivery system that allowed both oral administration and the
therapeutic efficacy, Solid Lipid Microparticles (SLMs) containing a theoretical 18% w/w of IAC
have been produced. Recently, three formulations (A, B, C) have been tested at different dosages
in an inflammation and pain rat model. Inflammatory model was induced by the use of an
intraplantar injection of 100ml/paw of Freund's complete adjuvant (FCA). Administered per os at
different dosages, IAC B (60% stearic acid-20% Compritol® HD5 ATO) was the most efficient
formulation in reducing oedema and alleviating pain, compared to the gold standard Paracetamol.
Since the anti-diabetic effects of the i.p. formulation of IAC was already demonstrated in vivo, we
are now investigating the therapeutic efficacy of the selected (B) oral IAC formulation (SLMs) in
streptozotocin-nicotinamide diabetic mice
Eudragit-coated albumin nanospheres carrying inclusion complexes for oral administration of indomethacin
No full textOral administration of indomethacin as well as drugs with low aqueous solubility usually results in poor absorption and bioavailability. The aim of this study was to prepare enteric-coated bovine serum albumin nanospheres carrying cyclodextrin complex for indomethacin delivery. Inclusion complex composed of indomethacin and β-cyclodextrin was prepared by spray-drying. Indomethacin alone and its inclusion complex were incorporated into albumin nanospheres using a coacervation method followed by thermal cross-linking. Then nanosphere suspensions were spray-dried. The inclusion complex and the nanospheres were characterized by FT-IR spectroscopy and DSC analysis. Phase-solubility diagrams and stability constants were determined at pH 2.0 and 7.4 and at different temperatures (10, 25 and 37°C). Swelling ability of nanospheres were evaluated as well as the in vitro release behaviour at pH 2.0 and 7.4. The nanospheres were coated with Eudragit L-100 or S-100 using spray-drying to give protection in the stomach. The results showed that indomethacin solubility can be increased by complexation with β-cyclodextrin or protein/drug interaction with albumin nanospheres. The inclusion complex loaded into BSA nanospheres provided a zero order drug release kinetic. The coating process with EudL and EudS allowed to obtain a negligible release at acidic pH without limit drug availability at pH 7.4
Preparation of gastroresistant mesalazine lipidic microcapsules
No full textINTRODUCTION AND OBJECTIVES
Mesalazine or 5-aminosalicylic (5-ASA), a typical antiinflatmmatory drug, is customarily used to maintain remission in inflammatory bowel disease (Carter, 2004). Mesalazine acts topically on the colonic mucosa: current 5-ASA delivery systems have been developed to avoid absorption of mesalazine in the small intestine, thereby delivering maximal amounts of the drug to colonic mucosa (Van den Mooter 2006). The aim of this work was to develop and characterize gastro-resistant multiparticulate system for mesalazine colon delivery in paediatric administration.
MATERIAL AND METHODS
Mesalazine was kindly supplied by Doppel (Cortemaggiore, Italy) and stearic acid was purchased by ACEF (Fiorenzuola, Italy). Carnauba wax (Produits Roche S.A. France) and Eudragit (Rhom Pharma, Germany) were also used. All other chemicals were of analytical grade.
The 5-ASA microcapsules were manufactured in two steps through the spray-congealing technique. In the first step the mesalazine was disperded in a solution of Eudragit L in isopropyl alcohol prepared under stirring at the tempetature of 70°C. The carnauba wax was added to the dispersion and the temperature was raised up until 95°C to evaporate the isopropyl alcohol and io melt the lipid. The melted mass was sprayed through the WPN nozzle at 3.0 bar. In the second step the microcapsules were obtained by disperding the 5-ASA cores in a low melting point lipid as stearic acid at the temperature around 70°C. At this temperature the microsphere did not melt and remained well dispersed in the liquid mass. The dispersion was sprayed with the WPN nozzle at 1.2 bar and the microcapsules were obtained.
The drug loading was determined by adding the samples to a simulated intestinal fluid (SIF) at pH 7.4 and heating up to 70°C or to 850C to melt the lipophilic carrier as stearic acid or carnauba wax, respectively. The process was carried out under magnetic stirring for 5 hours to extract completely the 5-ASA. The solution was filtered with microcellulose filter and then assayed by UV at 330 nm. The analysis was peformed in triplicate.
The lipid microcapsules were examined both under an optical stereomicroscope (Citoval 2. Jena, Germany) connected to a video camera (JVC, Tokyo, Japan) and Scanning Electron Microscopy (SEM, JSM 6400, Jeol Ltd. Tokyo, Japan).
Physical changes in microcapsules during heating were monitored by Hot Stage Microscopy (HSM). A hot plate
(FP 52 Mettler, Grefensee, Switzerland) connected to a temperature controller (FP 5 Mettler) was used ..........
National Park of Sibillini Mountains: soils and mosses used for the evaluation of trace elements.
No full textSoil depositions from airborne particles of Al, As, Cd, Cr, Cu, Hg, Ni, Pb, Zn, Pt, Pd and Rh in forty-four moss and soil samples have been evaluated using mosses and soil collected in the Monti Sibillini National Park. The concentration values of almost all of the elements studied in the moss samples demonstrated an environment with little anthropization. The soils revealed low concentrations of these elements, and thus are suitable for any type of use. Using both soil and moss in these analyses has made it possible to ascertain that for the most part of the elements studied, the depositions originated from the earth’s crust. Application of the Coefficient of Variation has contributed to understanding the diversity of the depositions in the entire area: the results indicate that, in fact, they are quite uniform. The information obtained in this study confirms that mosses can be used successfully to evaluate the soil deposition from airborne particles of persistent contaminants such as heavy metals
STUDY OF THE SOLID STATE OF INDOMETHACIN PARTICLES OBTAINED BY PSEUDO-EMULSION TECHNIQUE
No full textINTRODUCTION
The dissolution properties of a drug and its release from a solid dosage form have a basic impact on its bioavailability. Solving solubility problems is a major challenge for the pharmaceutical industry with developments of new pharmaceutical products, since nearly half of the active substances are either insoluble or poorly soluble in water and display resistance to being wetted by and dissolved into the fluid in the gastrointestinal tract (Patravale et al., 2004). Since the dissolution rate of a drug is a function of its intrinsic solubility and its particle size, studies with poorly soluble drugs have demonstrated that particle-size reduction to the sub-micron range can lead to an increase in dissolution rate and higher bioavailability. Over the last 10 years, nanoparticle engineering processes have been developed and reported for pharmaceutical applications, such as the nanosuspensions, used to formulate compounds that are insoluble in both water and oils and to reformulate existing drugs to remove toxicologically less favourable excipients (Kesisoglon et al. 2007, Kocbek et al., 2006).
In this work we aimed to test the efficiency of the technique of pseudo-emulsion to produce nanoparticles of indomethacin and evaluate how this technique affects the formation of indomethacin polymorphs. Nanoparticles were analyzed by means of size analysis, XRD, DSC, TGA, dissolution test.
MATERIALS AND METHODS
Indomethacin (Sigma Chemical, USA); Tween 80 (Kock Light Laboratories, LTD, England); Benzalkonium chloride (Carlo Erba, Milano, Italy); Stearic acid (Polichimica, Bologna, Italy); Eudragit® RS PO (Rohm Pharma Gmbh, Weiterstedt, Germany); Acetone; Phosphate buffer pH 7.4 ( Sörensen)
Preparation of nanoparticles – Two solutions were prepared separately. An aqueous solution, suitably cooled in an ice bath to prevent temperature increase, contained the surfactant mixture and was stirred using turbo-emulsifier Ultra Turrax T25; the aqueous solution was dropwise added of an organic solution containing indomethacin dissolved in acetone, by means of a peristaltic pump. The emulsion thus formed is left under magnetic and slow stirring for 24 h to allow evaporation of the solvent. Nanoparticles of the drug were recovered by ultra-centrifugation (Alc 4239R-CFC-free).
Powder X-ray diffraction (XRD) - To perform X-ray diffractometric analysis a Philips PW3719 diffractometer was used, controlled by a computer. Experimental conditions: Cu K_ radiation (X = 1.78896 A° ); 40 kV and 30 mA. Scanning interval: 5–50◦ 2θ; time per step: l s; graphite monochromator on the diffracted beam.
Differential scanning calorimetry - Thermal and thermogravimetric analyses were performed with an automatic thermal analyzer system Mettler FP80 HT Central Processor and FP85 TA Cell and TGA (851/SF/1100).
Solubility – Saturated aqueous solutions of the three different physical forms of indomethacin were left to equilibrate at 25° for 72 h. Determination of the solubility was carried out spectrophotometrically.
RESULTS AND DISCUSSION
An important step in the production of the nanoparticles with the pseudo-emulsion technique is their recovery from the reaction vessel, due to difficulties of filtration as well as evaporation of the solvent that leaves into the particle mass surfactants and inorganic salts used for the nanoparticles preparation. Ultracentrifugation demonstrated suitable to eliminate the solvent, followed by a leaching with water to dissolve foreign substances used for the preparation
Thermal analysis revealed that indomethacin, in the gamma form as starting material: following the treatment of pseudo-emulsion, undergoes to a polymorph transition. The drug transforms first into the alpha form and then progressively into an amorphous form: these changes are documented by the position of the melting endotherm peaks in DSC thermogram. In the amorphous form the area surface of the peak dramatically decrea..
Multifunctional liposomes for nasal delivery of the anti-Alzheimer drug tacrine hydrocloride
No full textThe purpose of this study was the development of multifunctional liposomes for nasal administration of tacrine hydrochloride. Liposomes were prepared using traditional excipients (cholesterol and phosphatidylcholine), partly enriched with a-tocopherol and/or Omega3 fatty acids. This approach was chosen in order to obtain at the same time two positive results: an enhanced drug permeation through nasal mucosa and a concomitant neuroprotective effect.
Several liposome formulations were prepared using the Reverse Phase Evaporation technique followed by membrane filter extrusion. In particular, liposome capacity to enhance drug permeation was evaluated by means of membrane permeation and cellular uptake studies.
Furthermore, liposome effect on neuronal viability and intracellular ROS production was evaluated as well as their cytoprotective effect against oxidative stress. All liposome
formulations showed a mean diameter in the range of 175nm to 219nm with polydispersity index lower than 0.22, a lightly negative zeta potential and excellent encapsulation efficiency.
Moreover, along with good mucoadhesive properties, multifunctional liposomes showed a markedly increase in tacrine permeability, which can be related to liposome fusion with cellular membrane, a hypothesis, which was also supported by cellular uptake studies. Finally, the addition of a-tocopherol without Omega3 fatty acids, was found to increase the neuroprotective activity and antioxidant properties of liposomes
A study for the development of the mesalazine multiparticulate dosage forms for colon delivery in paediatric patients.
No full textMesalazine (5-ASA) is an anti-inflammatory drug used for ulcerative colitis or Crohn's desease. Most of available oral 5-ASA dosage forms are modified release tablets targeting the colon. However, in paediatrics patient compliance would improve by avoiding dosage forms that channot be swallowed by children. The aim of this work was to develop gastro-resistant multiparticulate dosage forms for mesalazine colon delivery, for easier dose intake by children. Different granule formulations were considered starting from mesalazine granules prepared by kneading with an Eudragit S 100 solution and granulation (1 mm mesh sieve). Lipid coating was obtained by depositing melted stearic acid on 5-ASA granules. Lipid granules were also double coated by sprying on Eudragit FS suspension in a rotating glass pan.
Agglomerates were prepared by blending mesalazine lipid microparticles (manufactured by spray-congealing) with excipient microparticles, which had been separately obtained by spray-drying
A Study for the Development of Mesalazine Multiparticulate Dosage Forms for Colon Delivery in Pediatric Patients
No full textMesalazine (5-ASA) is an anti-inflammatory drug used for ulcerative colitis or Crohn’s disease. Most of available oral 5-ASA dosage forms are modified release tablets targeting the colon. However, in paediatrics patient compliance would improve by avoiding dosage forms that cannot be swallowed by children. The aim of this work was to develop gastro-resistant multiparticulate dosage forms for mesalazine colon delivery with easier dose intake by children
Primary antiphospholipid syndrome evolving into systemic lupus erythematosus: may antinucleosome antibodies be predictive?
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