Control of Transdermal Permeation of Hydrocortisone Acetate from Hydrophilic and Lipophilic Formulations

The purpose of this research was the preparation of four formulations containing hydrocortisone acetate (HCA) for topical application, including two aqueous systems (hydrophilic microemulsion and aqueous gel) and two systems with dominant hydrophobicity (hydrophobic microemulsion and ointment). The formulations were tested for the release and permeation of HCA across an animal membrane. The release of HCA was found comparable for the four systems. The two microemulsions promote permeation across an ex-vivo membrane, examined by means of a Franz cell. Hydrophobic microemulsion guarantees the highest solubility (2,370 μg/ml) and flux (133 μg/cm2.h) of the drug, since it contains almost 40% Transcutol, a permeation enhancer. Gel and ointment provide lower solubility and flux, being the values, related to the ointment, the lowest ones (562 μg/ml and 0.4 μg/cm2.h). Experimental results allow the conclusion that gel and ointment can be suitable when it is desirable to minimize absorption of topically applied HCA as to keep the drug restricted to the diseased area and prevent side effects of the systemic presence of HCA

Razvoj i in vitro vrednovanje puferiranog bioadhezivnog vaginalnog gela za miješane vaginalne infekcije

An acid buffering bioadhesive vaginal (ABBV) gel was developed for the treatment of mixed vaginal infections. Different bioadhesive polymers were evaluated on the basis of their bioadhesive strength, stability and drug release properties. Bioadhesion and release studies showed that guar gum, xanthan gum and hydroxypropylmethylcellulose K4M formed a good combination of bioadhesive polymers to develop the ABBV gel. Mono sodium citrate was used as an acid buffering agent to provide acidic pH (4.4). The drugs clotrimazole (antifungal) and metronidazole (antiprotozoal as well as antibacterial) were used in the formulation along with Lactobacillus spores to treat mixed vaginal infections. The ex vivo retention study showed that the bioadhesive polymers hold the gel for 12-13 hours inside the vaginal tube. Results of the in vitro antimicrobial study indicated that the ABBV gel had better antimicrobial action than the commercial intravaginal drug delivery systems and retention was prolonged in an ex vivo retention experiment.U radu je opisan razvoj puferiranog biodhezivnog vaginalnog (acid buffering bioadhesive vaginal, ABBV) gela za terapiju miješanih vaginalnih infekcija. Ispitani su različiti bioadhezivni polimeri procijenjena su njihova bioadhezivna svojstva, stabilnost i sposobnost oslobađanja ljekovite tvari. Guar guma, ksantan guma i hidroksipropilmetilceluloza K4M tvore dobru kombinaciju za ABBV gel. Mono natrijev citrat upotrebljen je kao puferirajuća tvar koja omogućava blago kiseli pH (4,4), a kao ljekovite tvari upotrebljeni su klotrimazol (antimikotik) i metronidazol (antiprotozoik i antibakterijsko sredstvo), zajedno sa sporama Lactobacillus. Pripravci su upotrebljeni u terapiji miješanih vaginalnih infekcija. Pokusi ex vivo pokazali su da se bioadhezivni gel zadržava u vagini 12-13 sati. Rezultati in vitro ispitivanja ukazuju na to da ABBV gel ima bolje antibakterijsko djelovanje i dulje zadržavanje od intravaginalnog sustava koji je dostupan na tržištu

Space-maintaining management in maxillary sinus lifting: a novel technique using a resorbable polymeric thermo-reversible gel

Several techniques have been proposed to achieve sinus floor elevation and the formation of new bone through the grafting of autologous, heterologous, or alloplastic materials. The grafted materials act as a scaffold for bone formation inside the maxillary sinus. This study investigated a non-graft sinus lifting procedure using a resorbable polymeric thermo-reversible gel. A space-maintaining approach to sinus lifting, using a resorbable polymeric thermo-reversible gel, was applied in 11 patients undergoing implant treatment in the atrophic posterior maxilla. After a healing period of 6 months, a total of 14 implants were placed; biopsies were taken and evaluated histologically and histomorphometrically. The parameters evaluated included the percentages of new bone formation, residual gel, and fibrous tissue. Histological examination showed the formation of new bone with no fibrous tissue or severe inflammatory cellular infiltration. The percentage of newly formed bone was in the range of 54\u201360%; this consisted of both lamellar and woven bone. No foreign-body reaction was observed. The mean quantities of both residual gel and connective tissue were small. This non-graft sinus lifting procedure using a space-maintaining gel appears to stimulate predictable bone formation; it is thus a useful technique for promoting bone formation in the sinus

Bimodal release of olanzapine from lipid microspheres

Olanzapine was formulated as 10% (w/w) mixture with cutina to which stearic acid was added, ranging from 10% to 90% (w/w) of the total mass to control the drug release. The molten mixtures were processed by ultrasound-assisted spray-congealing technique, obtaining solid microspheres. The drug is stable under these conditions and only a partial miscibility in the solid state was observed by DSC between the two fatty materials with two separated melting endotherms in the thermograms: this can be due to the presence of two phases inside the solid dispersion. Olanzapine is distributed into the two phases according to its partition coefficient: two phases make the system less suitable to crystallization of the drug; the loading of the drug could reach saturation with difficulty and the rate of the olanzapine release is differentiated, since the drug is released from two different carriers. Dissolution profiles suggest occurrence of a bimodal release, where each portion of the release profile is linear and the slope increases with a higher content of stearic acid in the carrier mixture, that behaves as a release promoter. Tests were also carried out with palmitic and lauric acids for comparison and also for systems in the absence of ultrasound

Analysis of all-in-one parenteral nutrition admixtures by liquid chromatography and laser diffraction: study of stability

All-in-one parenteral nutrition admixtures are complex lipid emulsions (oil:water) which require absolute sterility, stability and no precipitates. Particle diameter must be in the range 0.4\u20131 mm in order to mime the size of chylomicra. Added vitamins must not degrade during infusion time (24 h). In this study, the physicochemical stability of parenteral nutrition admixtures was tested in the course of time at different storage temperatures. Two liquid chromatographic methods, based on solid phase extraction (SPE), were developed for fat-soluble vitamin determination. Stability studies were carried out on three industrial lipid emulsions and on six compounded all-in-one admixtures. They were stored at three different temperatures: 4\ub0C (storage), 25\ub0C (compounding) and 37\ub0C (infusion); then they were analyzed at starting time and at 24, 48 and 72 h after compounding. Particle diameter was determined by means of Laser Particle Sizer Analysette 22, which uses laser diffraction technique (light scattering \u2014 reverse Fourier optics). Fat-soluble vitamins (retinol palmitate and a-, d-, g-tocopherol) were determined in admixtures with a branded vitamin compound called Idroplurivit\uae Liofilizzato. Samples were extracted by SPE on C18 cartridges, then they were separated by reversed-phase liquid chromatography (LC) and detected by ultraviolet detection (retinol palmitate) and electrochemical detection (tocopherols). Laser diffraction analysis pointed out that particle size did not change in the course of time at the tested temperatures. LC analysis showed that vitamins interact each other and degrade after compounding at different times and storage temperatures; only retinol palmitate is stable at 37\ub0C. Retinol palmitate recovery was 98%, coefficient of variation (CV) 5.4%, detection limit 25 mg:l, limit of quantitation 75 mg:l and there were not interfering substances. Tocopherols average recovery was 99%, CV 3.5%, detection limit 15 ng:l and limit of quantitation 50 ng:l. In conclusion, all-in-one parenteral admixtures were proved to be physically stable under analysis conditions, but degradation of retinol palmitate and tocopherols requires admixtures with vitamins to be infused within 24 h after compounding

Effect of Thermosetting Gel with Doxycycline Hyclate 3% + Ketorolac Tromethamine 0.5% on Postoperative Discomfort after Third Molar Surgery: A Prospective Randomized Study

This study compared the analgesic and anti-inflammatory efficacy of intra-alveolar administration of a thermosetting gel containing Doxycycline Hyclate 3% + Ketorolac Tromethamine 0.5% (Tg-DHKT) (Thermosetting gel, Monteresearch, Bollate, Italy) on patient discomfort after third molar surgery. This study was a single-blind, randomized clinical trial, including two study groups of 39 and 41 patients each, who required surgical removal of a single mandibular impacted third molar. After the extraction the test group received an intra-alveolar injection with Tg-DHKT and the second group a thermosetting gel containing only Doxycycline Hyclate 3% (Tg-DH). Each patient's symptoms (pain, swelling, reddening, bleeding and body temperature) was assessed with a follow-up questionnaire (PoSSe scale). Nimesulide 100 mg, a painkiller, every 8 hours was prescribed to the Control and Test groups if necessary (maximum 3 doses); if they needed to assume it they were asked to mark it on the questionnaire. Results showed that on the second day after surgery pain, oedema and reddening decreased faster in the Control group (Tg-DH). There was no difference between the two groups when postoperative bleeding was evaluated. In both groups bleeding decreased in the same way, probably due to the mechanical characteristics of the gel itself. 46% of patients of the Test group did not require to take any painkiller at home. Our data demonstrate that the use of Tg-DHKT is less effective in the prevention of postoperative symptoms after third molar extraction compared to Tg-DH. However, almost half of patients in the Test group did not need to take more pain medication at home, suggesting that a single postoperative local administration of Tg-DHKT is a safe and effective concept for controlling pain, oedema and inflammation after third molar extraction

MUCOADHESIVE GELS FOR BUCCAL ADMINISTRATION OF CHLORHEXIDINE DIGLUCONATE

Chlorhexidine (CHX) is a bis-bis-guanide widely used to treat skin and mucosa infections, efficient against a wide range of microbial species. The aim of this work was to design and evaluate gels containing CHX associated to mucoadhesive and swelling agents, such as CMC, HPMC, HPC and Poloxamer, to control both the residence time in the oral cavity and the release rate of the drug. Three tests were carried out to evaluate the controlled release of CHX from the gels; also the interaction polymer-mucin by means of viscosimetric measurements was tested. The same tests were also applied to a commercial formulation, Corsodyl gel® for comparison

MUCOADHESIVE GEL CONTAINING NAPHAZOLINE HYDROCHLORIDE FOR OPHTHALMIC DELIVERY

none6Naphazoline (NPH) is a vasoconstrictor agent, and reduces inflammation and swelling of the conjunctiva. The effect of naphazoline arises from its direct binding to adrenergic receptor sites on unstriated muscle cells in the blood vessels. A modern tendency of ocular delivery is represented by systems capable of both lengthening pre-cornea1 contact time and slowing the release of drug from the vehicle. There is considerable logic in attempting the retention of the delivery systems in the front of the eye, because of the enormous loss of an instilled drug solution that typically occurs soon after administration. In this study we present a low viscous formulation with mucoadesive properties to control the residence time in pre-corneal area and the release and permeation rates of drug.noneG.C. Ceschel; V. Bergamante; I. Orienti; G. Zuccari; C. Ronchi; A. FiniG.C. Ceschel; V. Bergamante; I. Orienti; G. Zuccari; C. Ronchi; A. Fin