International journal of pharmaceutics
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The aerosol properties of liposomes and their physical stability to aerosolization were evaluated using an air-jet nebulizer (Pari LC Plus) and a customized large aperture vibrating-mesh nebulizer (Aeroneb Pro-8microm). Soya phosphatidylcholine: cholesterol (1:1 mole ratio) multilamellar liposomes (MLVs) entrapping salbutamol sulfate were nebulized directly, or after being reduced in size by extrusion through 1 or 0.4microm polycarbonate membrane filters. MLVs were very unstable to jet nebulization and stability was not markedly enhanced when vesicles were extruded before nebulization, such that drug losses from delivered liposomes using the Pari nebulizer were up to 88% (i.e. only 12% retained in liposomes). ⋯ However, extrusion of liposomes to 0.4microm resulted in reduced stability of liposomes to vibrating-mesh nebulization (retained entrapment=41%) which was attributed to the reduced liposome lamellarity and subsequent reduced resistance to nebulization-induced shearing. This study has shown that vibrating-mesh nebulization using the customized large aperture mesh nebulizer (Aeroneb Pro-8microm) had a less disruptive effect on liposomes and produced a higher output rate compared with the Pari LC Plus air-jet nebulizer. On the other hand, the air-jet nebulizer produced higher total mass and drug outputs and smaller aerosol droplets.
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Local anesthetics are substances able to induce pain relief by binding to the sodium channel of excitable membranes, blocking the influx of sodium ions and the propagation of nervous impulses. S(--) bupivacaine (S(--) bvc) is an amide type local anesthetic widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. The present work focuses on the characterization of an inclusion complex of S(--) bvc in 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD). ⋯ In addition, the study of the apparent stability constant by HPLC and solubility isotherm gives thermodynamics information about the interaction between S(--) bvc and HP-beta-CD. The application of the continuous variation method indicated the presence of a complex with 1:1 S(--) bvc:HP-beta-CD stoichiometry. This is an important study for the characterization of potential formulations to be used as therapeutic options for the treatment of pain.
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The purpose of this study was to investigate the effect of morin on the pharmacokinetics of orally and intravenously administered paclitaxel in rats. Pharmacokinetic parameters of paclitaxel were determined in rats after an oral (30 mg kg(-1)) or intravenous (3 mg kg(-1)) administration of paclitaxel to rats in the presence and absence of morin (3.3 and 10 mg kg(-1)). Compared to the control given paclitaxel alone, pretreatment with morin 30 min prior to the oral administration of paclitaxel increased C(max) and AUC of paclitaxel by 70-90% and 30-70%, respectively, while there was no significant change in T(max) and terminal plasma half-life (T(1/2)) of paclitaxel. ⋯ In contrast, following an intravenous administration of paclitaxel (3.3 mg kg(-1)), the pharmacokinetic profiles of paclitaxel were not altered significantly in the presence of morin. Those results suggest that the enhanced oral exposure of paclitaxel should be mainly due to the inhibition effect of morin on the gastrointestinal extraction of paclitaxel during the intestinal absorption. Therefore, the concurrent use of morin or morin-containing dietary supplement may provide a therapeutic benefit in the oral delivery of paclitaxel.
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Glyceryl monooleate (GMO) is a polar amphiphilic lipid, which forms different sequential lyotropic liquid crystals upon hydration. GMO has been utilized for various delivery systems and routes of administrations. Owing to sticky and waxy nature of GMO, preparation of oral solid dosage form utilizing GMO is still a challenge for pharmaceutical researchers. ⋯ The drug released from powder precursor was initially governed by the cubic phase formed and in later stage it depends upon dynamic swelling behavior of hexagonally packed cylindrical aggregates. The drug loaded powder precursor was found to have more effective and prolonged anti-inflammatory and analgesic activity as compared to pure drug. Thus the dry powder precursor of cubic phase was prepared in which drug release was entirely governed by the mesophases formed.
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Transdermal drug delivery via iontophoresis is reviewed with special focus on the delivery of lidocaine for local anesthesia and fentanyl for patient controlled acute therapy such as postoperative pain. The role of the microprocessor controller in achieving dosimetry, alternating/reverse polarity, pre-programmed, and sensor-based delivery is highlighted. Unique features such as the use of tactile signaling, telemetry control, and pulsatile waveforms in iontophoretic drug delivery are described briefly.