1,721,022 research outputs found
Albuterol prodrugs for ocular administration: Synthesis and evaluation of the physico-chemical and IOP-depressant properties of three albuterol triesters
No full textThree albuterol (salbutamol) new triesters (acetyl, isobutyryl and pivalyl) were prepared and evaluated in vitro (rate of chemical hydrolysis at different pH values, relative lipophilicity) and in vivo (depression of intraocular pressure, IOP, in a rabbit model of ocular hypertension). The three esters underwent quantitative hydrolysis in vitro to give the parent compound: first-order kinetics were observed, for several half-lives, for the disappearance of the compounds from solution at different pH values. The degradation mechanism, presumably involving a sequence of hydrolytic steps, was not investigated in detail. The rate constants for disappearance of the triesters and for formation of albuterol were in the order acetyl > isobutyryl > pivalyl; the relative lipophilicities of the compounds, as estimated by the corresponding reversed phase HPLC 'capacity factors', were in the order albuterol < acetyl < isobutyryl < pivalyl. When tested for reduction of IOP, all three ester solutions proved significantly more active than albuterol at several times after administration. The tripivalyl ester, in particular, after 5 h appeared more active than the other two esters, and, together with the triisobutyryl ester, was significantly more active than the triacetate after 8 h. These findings confirm the.important influence of (pro)drug lipophilicity on transcorneal penetration. The in vivo tests also indicated that the ocular irritant properties of the parent drug were still present, albeit to a smaller degree, in the triester derivatives
ALKYLATION OF ADENOSINE DEAMINASE BY BENZYLBROMOACETATE AND 9-(PARA-BROMOACETAMIDOBENZYL)ADENINE
No full textAdenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) from calf intestinal mucosa is not affected at pH 8 by haloacetate and haloacetamide, while benzylbromoacetate and 9-(p-bromoacetamidobenzyl)adenine inactivate the enzyme. Substrate analogs protect against inactivation by these reagents. 2. 2. One mole of reagent is bound per mole of inactivated enzyme. The alkylated amino acid has been identified as lysine. 3. 3. The reaction of alkylation consists of two stages: binding of the alkylating agent (fast reaction) and alkylation of the ε-amino group of lysine (slow reaction). 4. 4. Bromoacetate, which does not inactivate the enzyme, does not alkylate the reactive lysine. 5. 5. The difference in reactivity is explained on the basis of a selectivity of the alkylation site on the enzyme towards the alkylating reagents
Ophthalmic emulsions and suspensions (Reprinted from Pharmaceutical Emulsions and Suspensions, pg 303-322, 2000)
No full textAlbumin microspheres for ocular delivery of piroxicam
No full textThis investigation deals with the preparation, in-vitro characterization and preliminary in-vivo evaluation of albumin microspheres containing piroxicam. The albumin piroxicam microspheres, designed for ocular administration, were prepared by a spray-drying technique. The morphological and dimensional characteristics of the particles were studied by scanning- electron microscopy and particle-size analysis. Their in-vitro release behaviour was investigated in pH 7-0 USP23 buffer by use of a flow-through apparatus. Piroxicam in the albumin microspheres dissolved more quickly in- vitro than did piroxicam powder. The pharmacokinetic profile of piroxicam in aqueous humour was investigated in albino rabbits. The albumin piroxicam microspheres resulted in greater bioavailability of piroxicam than commercial piroxicam eyedrops
Permeazione transungueale “in vitro” di ciclopirox da smalti medicati: effetto del tipo di veicolo
No full textPharmacokinetics and anti-inflammatory activity in rabbits of a novel indomethacin ophthalmic solution
No full textThe formulation of aqueous ophthalmic solutions containing indomethacin (IND) presents serious problems due to poor solubility and stability of the drug. The purpose of this study was to evaluate a novel 0.1% IND formulation containing a poly(oxyethylene)poly(oxypropylene) block copolymer (poloxamer 407) as solubilizer. This formulation was evaluated for stability, bioavailability and anti-inflammatory activity in comparison with an ophthalmic IND solution currently on the market. The experimental solution, tested for IND stability at different temperatures, compared favorably with the commercial solution. In rabbits, it produced significantly higher IND levels in the aqueous humor and, in an immunogenic uveitis model, it induced a comparatively faster resolution of the symptoms, as determined by inflammation scores and by IOP measurements. The data indicate poloxamer 407 as a potentially valuable nonirritating, solubilizing and stabilizing agent for indomethacin
Development of a novel polymeric formulation based on tamarind gum polysaccharide (TSP) for treatment of dry eye syndrome
No full textContemporary administration of pilocarpine and timolol increases the aqueous humor pilocarpine levels in the rabbit
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In vitro evaluation of some parameters involved in mucoadhesion of aqueous polymeric dispersions
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