Anti-inflammatory activity of linalool and linalyl acetate constituents of essential oils.

Linalool and linalyl acetate are the principal components of many essential oils known to possess several biological activities, attributable to these monoterpene compounds. In this work, we evaluated individually the anti-inflammatory properties of (-) linalool, that is, the natural occurring enantiomer, and its racemate form, present in various amounts in distilled or extracted essential oils. Because in the linalool-containing essential oils, linalyl acetate, is frequently present, we also examined the anti-inflammatory action of this monoterpene ester. Carrageenin-induced edema in rats was used as a model of inflammation. The experimental data indicate that both the pure enantiomer and its racemate induced, after systemic administration, a reduction of edema. Moreover, the pure enantiomer, at a dose of 25 mg/kg, elicited a delayed and more prolonged effect, while the racemate form induced a significant reduction of the edema only one hour after carrageenin administration. At higher doses, no differences were observed between the (-) enantiomer and the racemate; a further increase in the dose of both forms did not result in an increased effect at any time of observation. The effects of equi-molar doses of linalyl acetate on local edema were less relevant and more delayed than that of the corresponding alcohol. These finding suggest a typical pro-drug behavior of linalyl acetate. The results obtained indicate that linalool and the corresponding acetate play a major role in the anti-inflammatory activity displayed by the essential oils containing them, and provide further evidence suggesting that linalool and linalyl acetate-producing species are potentially anti-inflammatory agents.

Spray-dried microspheres containing ketoprofen formulated into capsules and tablets.

In this study, microspheres were prepared by a spray-drying technique using solutions of ketoprofen and two polymers, cellulose acetate butyrate (CAB) and hydroypropylmethylcellulose phthalate (HPMCP), in different weight ratios. Different total concentrations were used in the feed solutions: 3, 6 and 9% w/v. The spray-dried microparticles were characterized in terms of shape (SEM), size (light scattering method), production yield and encapsulation efficiency. They were formulated into capsules; tablets were prepared by direct compression of the microparticles mixed with maltose and, in some cases, hydroypropylmethylcellulose (HPMC). In vitro release studies were performed both at acidic and neutral pHs. The spray-drying process of solutions of ketoprofen with polymeric blends of cellulose derivatives leads to microparticles which, depending on their final formulation (capsules or tablets), can give a rapid or prolonged drug release. The formulations here described can be proposed for the oral administration of NSAIDs.

In vitro release and antiinflammatory activity of topical formulations of ketoprofen.

Ketoprofen (KP) is a potent nonsteroidal anti-inflammatory drug (NSAID) widely used in clinical practice for the control of acute and chronic pain of soft tissues and skeletal muscle system. The importance of KP in the therapeutic field, has stimulated the development of topical dosage forms to improve its percutaneous absorption through the application site. Moreover they could provide relatively consistent drug levels for prolonged periods and avoid gastric irritation, typical side effect of NSAID oral administration. Since the topical formulation efficiency depends on vehicle characteristics, some different ointments, at 1% and 5% concentrations of KP, were evaluated by in vitro and in vivo studies. Among tested ointments, 1% Carbopol cream and 5% Carbopol gel showed the best fluxes of drug through regenerated cellulose membrane. The in vivo percutaneous absorption of KP, evaluated by carrageenan-induced paw edema in rats, showed a good correlation with the in vitro results about considered creams, but the gels in vivo activity was not in according to their in vitro behaviour. The extemporaneous Carbopol cream was able to produce a better edema inhibition than the commercial one, taken as a reference and widely utilized as a topical therapeutic item. About gels, the obtained results were nearly the maximum response considered possible for a topical antiinflammatory drug.

In vitro permeation through porcine buccal mucosa of Salvia desoleana Atzei & Picci essential oil from topical formulations.

In the light of recent studies, which have shown that the essential oil derived from some Lamiaceae species has appreciable anti-inflammatory activity, moderate anti-microbial action and the ability to inhibit induced hyperalgesia, an assessment of the diffusion and permeation of Salvia desoleana Atzei & Picci (S. desoleana) essential oil through porcine buccal mucosa was considered useful for a possible application in the stomatological field. Topical formulations (microemulsions, hydrogels and microemulsion-hydrogels) were prepared for application to the buccal mucosa. The mucosa permeation of the oil from the formulations was evaluated using Franz cells, with porcine buccal mucosa as septum between the formulations (donor compartment) and the receptor phase chambers. The study also aimed at optimising the permeability of the S. desoleana essential oil by means of an enhancer, the diethylene glycol monoethyl ether Transcutol. The diffusion of the oil through the membrane was determined by evaluating the amount of essential oil components present in the receiving solution, the flux and the permeation coefficient (at the steady state) in the different formulations at set intervals. Qualitative and quantitative determinations were done by gas chromatographic analysis. All the formulations allow a high permeability coefficient in comparison with the pure essential oil. In particular, the components with a terpenic structure (beta-pinene, cineole, alpha-terpineol and linalool) have the highest capacity to pass through the porcine buccal mucosa when compared to the other components (linalyl acetate and alpha-terpinil acetate). Moreover, the enhancer, diethylene glycol monoethyl ether largely increases the permeation of the essential oil components in relation to the concentration.

Evaluation of alginate compressed matrices as prolonged drug delivery systems.

This research investigated the use of sodium alginate for the preparation of hydrophylic matrix tablets intended for prolonged drug release using ketoprofen as a model drug. The matrix tablets were prepared by direct compression using sodium alginate, calcium gluconate, and hydroxypropylmethylcellulose (HPMC) in different combinations and ratios. In vitro release tests and erosion studies of the matrix tablets were carried out in USP phosphate buffer (pH 7.4). Matrices consisting of sodium alginate alone or in combination with 10% and 20% of HPMC give a prolonged drug release at a fairly constant rate. Incorporation of different ratios of calcium gluconate leads to an enhancement of the release rate from the matrices and to the loss of the constant release rate of the drug. Only the matrices containing the highest quantity of HPMC (20%) maintained their capacity to release ketoprofen for a prolonged time.

Chemical composition and antimicrobial action of the essential oils of Salvia desoleana and S. sclarea.

The chemical composition of the essential oils of Salvia desoleana Atzei & Picci and Salvia sclarea L. from Sardinia (Italy) was analysed by GC and GC/MS. S. desoleana oil had a high content of monoterpenic esters (linalyl acetate and alpha-terpinyl acetate) and a lower amount of the corresponding alcohols while S. sclarea oil was characterised by a higher content of alcohols and lower quantity of esters. We studied the antimicrobial activity of these oils concerning their use in pharmaceutical preparations for local application. Only weak microbiostatic inhibitory activity was seen against S. aureus, E. coli, S. epidermidis and C. albicans, but since inhibition increased progressively with contact time, better results could be obtained by using these oils in bioadhesive formulations that would also have anti-inflammatory and peripheral analgesic action at a local level, as demonstrated in experimental animals following systemic application.

Anti-inflammatory activity of aqueous extracts and steroidal sapogenins of Agave americana.

Lyophilized aqueous extracts obtained from Agave americana L (Agavaceae) collected in the north of Sardinia were characterized with regard to their steroidal sapogenin content. Extracts of A. americana and genins isolated from them were evaluated for anti-inflammatory properties by testing their effects on carrageenin-induced edema. The effect of orally administered genins on gastric mucous membranes was also assessed. Lyophilized extracts administered by the intraperitoneal route at doses equivalent to 200 and 300 mg/kg of fresh plant starting material, showed good anti-inflammatory activity. Doses of genins (total steroidal sapogenins, hecogenin and tigogenin) equivalent to the amount in the lyophilized extracts produced an antiedentatous effect which was much stronger and more efficacious than that obtained with an i.p. administration of 5 mg/kg of indomethacin or dexamethasone 21-phosphate at a dose equivalent to the molar content of hecogenin administered. At the doses used to evaluate the anti-inflammatory activity, the genins did not have any harmful effect on the gastric mucous membranes. Lesions occurred when significantly higher doses of hecogenin were given, but gastric damage was still less than that caused by the drugs used for comparative purposes.

Cyclopenta[e] [1,5] benzodiazepin-10 (9H)-one derivatives as CNS depressant agents.

A series of dialkylaminoalkyl derivatives of cyclopenta[e] [1,5] benzodiazepin-10(9H)-one (E1-4) and its 6-chloro derivative (E5-8) was prepared to evaluate their CNS activity in comparison with that of isosteric pyridodiazepinones (A1-4) previously described. The results of the pharmacological screening show a significant depressant activity more remarkable in 6-chloro derivatives, which also revealed a high and lasting analgesic activity. The replacement of pyridine with benzene nucleus did not show any significant or homogeneous activity variation.

Cyclopentenyl ethylamines active on CNS.

Two new cyclopentenylethylamines were prepared and were submitted to a pharmacological screening together with some others previously described and now reprepared. All compounds exhibited different degrees of depressive activity on CNS and good analgesic activity. Compound 5, bearing a phenyl group on the carbon atom to which the amino group is connected, appears rather interesting being the most active as analgesic and the least toxic. Compounds 2 and 3 are able to antagonize in a certain degree lethal doses of physostigmine and also, respectively, of pentylenetetrazole and strychnine.