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ABSTRACT: Thermal ink-jet spray freeze-drying (TIJ-SFD) was used to produce inhalable particles of terbutaline sulphate, the aerosolisation properties of which were compared to the commercial Bricanyl® formulation. Scanning electron micrograph images showed the particles to be spherical, highly porous and suitable for aerosolisation from a simple, capsule-based dry-powder device (Cyclohaler®) without the need for additional excipients. Particle size was dependent upon the concentration of solution jetted, as well as the distance between the print head and the surface of the liquid nitrogen. Starting with a 5% (w/v) solution and maintaining this distance at 3cm produced spherical, porous particles of volume median diameter 14.1±0.8μm and mass median aerodynamic diameter (MMAD) 4.0±0.6μm. The fine particle fraction (proportion of aerosol with MMAD≤4.46μm) was 22.9±3.3%, which compared favourably with that of the marketed dry powder inhaler formulation of terbutaline (Bricanyl® Turbohaler®; 25.7±3.8%), tested under the same conditions. These findings show that TIJ-SFD is a useful tool to predict the viability of a DPI formulation during preformulation physicochemical characterisation.
International journal of pharmaceutics 02/2013; 447:165-170. · 2.96 Impact Factor
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ABSTRACT: Nucleotides and nucleosides are not only involved in cellular metabolism but also act extracellularly via P1 and P2 receptors, to elicit a wide variety of physiological and pathophysiological responses through paracrine and autocrine signalling pathways. For the first time, we have used an ion-pair reversed-phase high-performance liquid chromatography ultraviolet (UV)-coupled method to rapidly and simultaneously quantify 12 different nucleotides and nucleosides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, adenosine, uridine triphosphate, uridine diphosphate, uridine monophosphate, uridine, guanosine triphosphate, guanosine diphosphate, guanosine monophosphate, guanosine): (1) released from a mouse renal cell line (M1 cortical collecting duct) and (2) in human biological samples (i.e., urine). To facilitate analysis of urine samples, a solid-phase extraction step was incorporated (overall recovery rate ≥ 98 %). All samples were analyzed following injection (100 μl) into a Synergi Polar-RP 80 Å (250 × 4.6 mm) reversed-phase column with a particle size of 10 μm, protected with a guard column. A gradient elution profile was run with a mobile phase (phosphate buffer plus ion-pairing agent tetrabutylammonium hydrogen sulfate; pH 6) in 2-30 % acetonitrile (v/v) for 35 min (including equilibration time) at 1 ml min(-1) flow rate. Eluted compounds were detected by UV absorbance at 254 nm and quantified using standard curves for nucleotide and nucleoside mixtures of known concentration. Following validation (specificity, linearity, limits of detection and quantitation, system precision, accuracy, and intermediate precision parameters), this protocol was successfully and reproducibly used to quantify picomolar to nanomolar concentrations of nucleosides and nucleotides in isotonic and hypotonic cell buffers that transiently bathed M1 cells, and urine samples from normal subjects and overactive bladder patients.
Purinergic Signalling 06/2012; 8(4):741-51. · 3.16 Impact Factor
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ABSTRACT: Crosslinked chitosan nanoparticles, prepared using ionic gelation, have been successfully formulated into pressurized metered dose inhalers (pMDIs) with potential for deep lung delivery of therapeutic agents. Nanoparticles were prepared from crosslinked chitosan alone and incorporating PEG 600, PEG 1000 and PEG 5000 for dispersion in aerosol propellant, hydrofuoroalkane (HFA) 227. Spherical, smooth-surfaced, cationic particles of mean size less than 230 nm were produced. Nanoparticles were positively charged and non-aggregated at the pH of the airways. Crosslinked chitosan-PEG 1000 nanoparticles demonstrated greatest dispersibility and physical stability in HFA-227, whereas other formulations readily either creamed or sedimented. Following actuation from pMDIs, the fine particle fraction (FPF) for crosslinked chitosan-PEG 1000 nanoparticles, determined using a next generation impactor, was 34.0±1.4% with a mass median aerodynamic diameter of 4.92±0.3 μm. The FPFs of crosslinked chitosan, crosslinked chitosan-PEG 600 and crosslinked chitosan-PEG 5000 nanoparticles were 5.7±0.9%, 11.8±2.7% and 17.0±2.1%, respectively. These results indicate that crosslinked chitosan-PEG 1000-based nanoparticles are promising candidates for delivering therapeutic agents, particularly biopharmaceuticals, using pMDIs.
European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 01/2012; 81(1):74-81. · 3.15 Impact Factor
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ABSTRACT: The use of thermal ink-jet spray freeze-drying (TIJ-SFD) to engineer inhalable, excipient-free salbutamol sulphate (SS) particles was assessed. A modified Hewlett-Packard printer was used to atomise aqueous SS solutions into liquid nitrogen. The frozen droplets were freeze-dried. It was found that TIJ-SFD could process SS solutions up to 15%w/v; the porous particles produced had a physical diameter of ca. 35 μm. Next generation impactor (NGI) analysis indicated that the particles had a smaller aerodynamic size (MMAD ranging from 6 to 8.7 μm). Particles prepared from the lowest concentration SS solution were too fragile to withstand aerosolisation, but the 5%w/v solution yielded particles having the best combination of strength and aerodynamic properties. Comparison with a commercial SS formulation (Cyclocap®) showed that the SFD preparation had an almost equivalent FPF (6.4 μm) when analysed with a twin-stage impinger (TSI; 24.0 ± 1.2% and 26.4 ± 2.2%, respectively) and good performance when analysed with NGI (FPF (4.46 μm):16.5 ± 2.0 and 27.7 ± 1.7, respectively). TIJ-SFD appears to be an excellent method to prepare inhalable particles. It is scalable yet allows assessment of the viability of the pulmonary route early in the development since it can be used with very small volumes (<0.5 mL) of solution.
European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 01/2012; 80(1):149-55. · 3.15 Impact Factor
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ABSTRACT: Whilst some proteins can be effectively administered to the lungs using a nebulizer, others, such as lactate dehydrogenase (LDH) are degraded during air-jet nebulization. In order to deliver LDH by nebulization a protective delivery system or carrier may therefore be appropriate. The aim of this study was to produce and characterize a formulation of LDH, which retains enzyme activity during nebulization. Chitosan, a biocompatible, biodegradable and bioadhesive polysaccharide polymer, was included in the formulations studied as a potential protective agent. Complexes of LDH with chitosan of different molecular weights and concentrations were assessed for size, zeta potential, aerosol droplet size and delivery from a jet nebulizer. The highest molecular weight chitosan had the greatest complex size and a net positive charge of +29.7mV. Jet nebulization resulted in aerosol droplets with median size in the range 2.36-3.52μm. Nebulization of LDH solution resulted in enzyme denaturation and reduced activity. The stability of LDH was greatly improved in formulations with chitosan; with greater than 50% total LDH available in a nebulizer delivered to the lower stage of a two-stage impinger, with up to 62% retained enzyme activity. The nonionic surfactant Tween 80 also improved the stability of LDH to nebulization and had an additive protective effect when included, with chitosan, in formulations. These findings suggest chitosan may be a useful excipient in the preparation of stable protein formulations for jet nebulization.
International journal of pharmaceutics 10/2010; 402(1-2):140-5. · 2.96 Impact Factor
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ABSTRACT: The aim of this study was to produce and characterise amphotericin B (AmB) containing chitosan-coated liposomes, and to determine their delivery from an air-jet nebuliser.
Soya phosphatidylcholine : AmB (100 : 1) multilamellar vesicles were generated by dispersing ethanol-based proliposomes with 0.9% sodium chloride or different concentrations of chitosan chloride. These liposomes were compared with vesicles produced by the film hydration method and micelles. AmB loading, particle size, zeta potential and antifungal activity were determined for formulations, which were delivered into a two-stage impinger using a jet nebuliser.
AmB incorporation was highest for liposomes produced from proliposomes and was greatest (approximately 80% loading) in chitosan-coated formulations. Following nebulisation, approximately 60% of the AmB was deposited in the lower stage of the two-stage impinger for liposomal formulations, for which the mean liposome size was reduced. Although AmB loading in deoxycholate micellar formulations was high (99%), a smaller dose of AmB was delivered to the lower stage of the two-stage impinger compared to chitosan-coated liposomes generated from proliposomes. Chitosan-coated and uncoated liposomes loaded with AmB had antifungal activities against Candida albicans and C. tropicalis similar to AmB deoxycholate micelles, with a minimum inhibitory concentration of 0.5 microg/ml.
This study has demonstrated that chitosan-coated liposomes, prepared by an ethanol-based proliposome method, are a promising carrier system for the delivery of AmB using an air-jet nebuliser, having a high drug-loading that is likely to be effectively delivered to the peripheral airways for the treatment of pulmonary fungal infections.
The Journal of pharmacy and pharmacology. 07/2010; 62(7):821-8.
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ABSTRACT: The aim of this study was to examine the use of continuing professional development (CPD) portfolios by hospital pharmacists. The objectives were to assess the extent to which pharmacists use portfolios in CPD and to examine the attitudes/beliefs which differentiate those who do and do not keep a portfolio.
Participants completed two questionnaires: (1) personality traits were examined using the Big-Five questionnaire and (2) a new Pharmacist Portfolio-Engaging Behaviour Questionnaire (PPEBQ) examined the attitudes and beliefs. What constitutes a portfolio was left to the interpretation of the participants, but it was specified that the survey was about participants' views of producing written records of their professional practice for CPD. The setting was hospital pharmacists based in the London area in December 2004.
Overall, 134 pharmacists (78%) returned both questionnaires, and 80 stated that they kept a portfolio and 52 stated that they did not (two questionnaires were returned spoilt). There was no significant difference in the age or number of years qualified between those with and without a portfolio. Three personality traits were linked to keeping a portfolio (conscientiousness, agreeableness and emotional stability). Pharmacists with a portfolio scored highly on the perceived behavioural control and behavioural intention scales of the PPEBQ.
The Big-Five personality questionnaire is a useful tool to investigate pharmacists' use of a portfolio. Results of the PPEBQ suggested that hospital pharmacists who had a portfolio were concerned with having control over its production. However, the PPEBQ requires further development to improve its reliability. These findings have implications for the educational support of CPD.
International Journal of Pharmacy Practice 10/2009; 17(5):299-304.
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ABSTRACT: Nanoparticles delivered from pressurized metered dose inhalers (pMDIs) potentially offer a means of efficiently delivering proteins to the lung. Nanoparticles containing the model protein lysozyme have been produced using microemulsion and nanoprecipitation methods. Freeze-drying water in oil emulsions, with chloroform as the organic solvent, followed by washing of excess surfactant (lecithin) led to the production of lactose nanoparticles having approximately 300 nm mean size. Substitution of lactose with lysozyme led to a significant increase in the mean size of nanoparticles (645-750 nm). This may have been due to the surface activity of lysozyme which altered the emulsification properties. The retained biological activity of lysozyme increased with increased lactose concentration in the formulation, and approximately 99% biological activity was retained when 20% (w/w) lactose was used. Ethanol used in the formulation in place of chloroform changed the production process from emulsification to nanoprecipitation. A monodisperse system (mean size approximately 275 nm, polydispersity index approximately 0.1) of spherical nanoparticles containing 80% (w/w) bioactive lysozyme (retained activity 99%) was generated. The nanoparticles washed with ethanol containing DPPC, oleic acid or Span 85 (2%, w/v) could readily be dispersed in HFA 134a without further processing, and a stable suspension was formed. Lysozyme remained stable (retained biological activity 98%) even after the nanoparticles were suspended in HFA 134a. This indicates the potential of nanoparticles for delivery of proteins from HFA-based pressurized metered dose inhaler formulations.
International journal of pharmaceutics 06/2009; 372(1-2):140-6. · 2.96 Impact Factor
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ABSTRACT: Nanoparticles containing insulin have been produced by emulsification processes followed by freeze-drying. Purified nanoparticles were suspended in hydrofluoroalkane (HFA) 134a, using essential oils (cineole and citral) as suspension stabilizers to form pressurized metered dose inhaler (pMDI) formulations. The retention of insulin integrity after formulation processing was determined using high performance liquid chromatography (HPLC), size exclusion chromatography (SEC), circular dichroism (CD) and fluorescence spectroscopy. The results indicated that the native structure of insulin was retained after formulation processing. Aerosolization properties of the manufactured pMDI formulations were determined using a multi-stage liquid impinger. The results showed that the nanoparticles were suitable for peripheral lung deposition, with a fine particle fraction (FPF(<1.7 microm)) of approximately 45% (w/w). In conclusion, the pMDI formulations with nanoparticles containing insulin developed in this study have the potential to deliver protein therapeutics via inhalation for systemic action.
International journal of pharmaceutics 06/2009; 375(1-2):114-22. · 2.96 Impact Factor
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ABSTRACT: The aim of this study was to undertake an in-depth investigation of the influence of continuing professional development (CPD) portfolios on pharmacy practice in the hospital setting. The objectives were to explore the views of pharmacists regarding the contribution of CPD records to professional practice and examine the influence of time and experience on pharmacists' views of recording professional practice.
A qualitative design was used to explore the views of pharmacists over 12 months. Pharmacists were stratified according to years of practice in the UK National Health Service (NHS). The methods used involved semi-structured in-depth face-to-face interviews. The interviews were undertaken at three time points. The pharmacists were gathered into three focus groups to test the consistency of the interviews. A purposive sampling method used nine NHS Teaching and Non-Teaching hospital pharmacists in the London area.
The participants included four males and five females, who had been qualified for between 0.1 and 21 years. Three key themes emerged for how CPD records contribute to practice: (1) lack of contribution to practice, (2) tacit contribution and (3) mentality. Overall, the recording process made little if any change in professional practice. The more experienced participants were less likely to be able to explain any changes in practice and there were no consistent changes in the views expressed over time.
The contribution of CPD recording to enhancing practice in hospital pharmacists was difficult to demonstrate. This study has also illustrated the power relationships involving control mechanisms used by the NHS, and the UK pharmacists' regulatory body, which are discussed in the context of the Panopticon model of self-regulated behaviour. Further research is needed to establish the value of CPD recording.
International Journal of Pharmacy Practice 04/2009; 17(2):107-13.
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International Journal of Pharmacy Practice. 12/2008; 16.
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ABSTRACT: We report the appearance of 'poppy seed'-like structures found in the aspirated stomach contents and faeces of a 3-month-old infant receiving an omeprazole liquid via nasogastric tube, prepared by dispersing an omeprazole tablet (10 mg MUPS(R)) in water. Electron microscopy and mass spectroscopy indicated that these particles were hollow, dark purple coloured spheres comprising undissolved omeprazole and its degradation products. These observations suggest rapid degradation of omeprazole in the acid stomach contents, with compromised absorption of active drug. Consequently, dispersion of omeprazole in water may be an inappropriate formulation in this setting.
European Journal of Pediatrics 08/2008; 167(7):823-5. · 1.88 Impact Factor
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ABSTRACT: Insulin adsorption onto infusion equipment may affect glycaemic control.
The change in insulin concentration during delivery through tubing employed for adult ICU and neonatal patients was determined using continuous flow UV analysis.
Insulin adsorption depended on tubing composition, dimensions and flow rate, being highest for neonatal polyvinylchloride tubing at low flow rates.
In continuous insulin therapy, we should consider the nature of the infusion set and flow rate.
Diabetes research and clinical practice 07/2008; 80(3):e11-3. · 2.16 Impact Factor
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ABSTRACT: To investigate plasmid DNA interactions with liposomes prepared from dimyristoylglyceroethylphosphocholine (EDMPC) and DOPE using high sensitivity differential scanning calorimetry (HSDSC).
Large unilamellar liposomes of EDMPC with DOPE (mol ratio 0-50%) were prepared. Plasmid DNA was added to give a final DNA/lipid (-/+) charge ratio of 0.5. Samples were placed into an HSDSC and cooled to 3 degrees C, held isothermally for 30 min and then the temperature was ramped to 120 degrees C at a rate of 1 degree C/min.
On heating EDMPC liposomes, the main phase transition occurred at 21.2 degrees C, with a low temperature shoulder on the endothermic peak. At low DOPE concentrations the main phase transition temperatures and enthalpies of transition were lower than for pure EDMPC, with a peak corresponding to a pure EDMPC phase occurring at DOPE concentrations of 12-17 mol%. At 50 mol%, no main transition endotherm was observed. DNA solution produced two endothermic peaks with numerous 'satellite' peaks indicating thermal denaturation. DNA binding to EDMPC changed the shape of the thermogram, indicating alteration in lipid packing within the bilayer. DNA induced demixing in the bilayers of DOPE-containing liposomes.
HSDSC provided information for characterizing liposome formulations and DNA interactions with such vesicles.
Pharmaceutical Research 11/2007; 24(10):1954-61. · 4.09 Impact Factor
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ABSTRACT: In this study, the effect of fluid physicochemical properties and the vibrating-mesh mechanism on the aerosols generated from vibrating-mesh nebulizers have been evaluated using fluids having a range of viscosity, surface tension and ion concentration. Two nebulizers were investigated: the Omron MicroAir NE-U22 (passively vibrating) and the Aeroneb Pro (actively vibrating) mesh nebulizers. For both devices, the total aerosol output was generally unaffected by fluid properties. Increased viscosity or ion concentration resulted in a decrease in droplet volume median diameter (VMD) and an increase in fine particle fraction (FPF). Moreover, increased viscosity resulted in prolonged nebulization and reduced output rate, particularly for the Omron nebulizer. Both nebulizers were unsuitable for delivery of viscous fluids since nebulization was intermittent or completely ceased at >1.92cP. The presence of ions reduced variability particularly for the Aeroneb Pro nebulizer. No clear effect of surface tension was observed on the performance of nebulizers employing a vibrating-mesh technology. However, when viscosity was low, reduced surface tension seemed advantageous in shortening the nebulization time and increasing the output rate, but for the Omron nebulizer this also increased the droplet VMD and decreased the FPF. This study has shown that vibrating-mesh nebulization was highly dependent on fluid characteristics and nebulizer mechanism of operation.
International Journal of Pharmaceutics 07/2007; 339(1-2):103-11. · 3.35 Impact Factor
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ABSTRACT: Multilamellar and oligolamellar liposomes were produced from ethanol-based soya phosphatidyl-choline proliposome formulations by addition of isotonic sodium chloride or sucrose solutions. The resultant liposomes entrapped up to 62% of available salbutamol sulfate compared with only 1.23% entrapped by conventionally prepared liposomes. Formulations were aerosolized using an air-jet nebulizer (Pari LC Plus) or a vibrating-mesh nebulizer (Aeroneb Pro small mesh, Aeroneb Pro large mesh, or Omron NE U22). All vibrating-mesh nebulizers produced aerosol droplets having larger volume median diameter (VMD) and narrower size distribution than the air-jet nebulizer. The choice of liposome dispersion medium had little effect on the performance of the Pari nebulizer. However, for the Aeroneb Pro small mesh and Omron NE U22, the use of sucrose solution tended to increase droplet VMD, and reduce aerosol mass and phospholipid outputs from the nebulizers. For the Aeroneb Pro large mesh, sucrose solution increased the VMD of nebulized droplets, increased phospholipid output and produced no effect on aerosol mass output. The Omron NE U22 nebulizer produced the highest mass output (approx. 100%) regardless of formulation, and the delivery rates were much higher for the NaCl-dispersed liposomes compared with sucrose-dispersed formulation. Nebulization produced considerable loss of entrapped drug from liposomes and this was accompanied by vesicle size reduction. Drug loss tended to be less for the vibrating-mesh nebulizers than the jet nebulizer. The large aperture size mesh (8 mum) Aeroneb Pro nebulizer increased the proportion of entrapped drug delivered to the lower stage of a twin impinger. This study has demonstrated that liposomes generated from proliposome formulations can be aerosolized in small droplets using air-jet or vibrating-mesh nebulizers. In contrast to the jet nebulizer, the performance of the vibrating-mesh nebulizers was greatly dependent on formulation. The high phospholipid output produced by the nebulizers employed suggests that both air-jet and vibrating-mesh nebulization may provide the potential of delivering liposome-entrapped or solubilized hydrophobic drugs to the airways.
Journal of Pharmacy and Pharmacology 08/2006; 58(7):887-94. · 2.17 Impact Factor
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ABSTRACT: The effect of pH on the adsorption of catalase and lysozyme at the air-water interface has been studied using a combined surface pressure-interfacial shear rheology technique. The results presented show that the rate of development of interfacial phenomena increases as the pH of the subphase approaches the isoelectric point of the protein under investigation. The development of the measured interfacial rheological parameters is due to an increased rate of cross-link formation within the resultant interfacial gel. The formation of the interfacial gels has been modeled using a combination of the Smoluchowski theory for the coagulation of an aerosol or fog and classic rubber elasticity theory. The enhanced rate of cross-link formation at the isoelectric point is a result of an in-surface phase separation brought about by cooperative deionization of the protein molecules near their isoelectric point. Simultaneous measurements of surface pressure and interfacial rheology have enabled us to show that the development of a gel-like interfacial network coincides with observed increases in surface pressure.
Langmuir 09/2005; 21(16):7342-8. · 4.19 Impact Factor
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ABSTRACT: The adsorption of two model proteins, catalase and lysozyme, to phospholipid monolayers spread at the air-water interface has been studied using a combined surface pressure-interfacial shear rheology technique. Monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DPPG) and DPPC:DPPG (7:3) were spread on a phosphate buffer air-water interface at pH 7.4. Protein solutions were introduced to the subphase and the resultant changes in surface pressure and interfacial storage and loss moduli were recorded with time. The results show that catalase readily adsorbs to all the phospholipid monolayers investigated, inducing a transition from liquid-like to gel-like rheological behaviour in the process. The changes in surface rheology as a result of the adsorption of catalase increase in the order DPPC<DPPC:DPPG<DPPG. Lysozyme behaves in a similar manner beneath a DPPG monolayer, but shows no measurable differences when injected beneath DPPC or the DPPC:DPPG (7:3) mixed monolayer. It is proposed that DPPG monolayers are more susceptible to penetration by adsorbing protein molecules. The interaction between DPPG and lysozyme is further enhanced due to electrostatic interactions between the negatively charged DPPG and the positively charged lysozyme.
International Journal of Pharmaceutics 09/2005; 300(1-2):48-55. · 3.35 Impact Factor
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ABSTRACT: The interaction of dimyristoylphosphatidylcholine (DMPC) with non-ionic surfactants has been studied using isoperibol calorimetry. Phospholipid-surfactant systems were formed in the isoperibol calorimeter with varying amounts of surfactant and the change in enthalpy on formation was measured. Solubilization of the phospholipid lamellae was assessed as a decrease in the enthalpy of reaction of co-films containing DMPC and increasing amounts of three linear alcohol ethoxylate surfactants: C(10)H(21)(OCH(2)CH(2))(3)OH, C(10)H(21)(OCH(2)CH(2))(5)OH, or C(12)H(25)(OCH(2)CH(2))(7)OH. The isoperibol calorimetry data for DMPC/surfactant/water systems were consistent with a theoretical three-stage model for the solubilization of phospholipids by surfactants, whereby phospholipid bilayers are transformed into mixed micelles with increasing amounts of surfactant. The results indicate that: (i) the interaction between phospholipid and surfactants results in a non-linear correlation between the enthalpy of reaction and the surfactant concentration; (ii) the structural stage of the lamellar to micelle transition (mixed bilayers, mixed micelles, or both) can be determined from calorimetric data; (iii) phase boundaries in the solubilization process (bilayer saturation, micelle saturation) can be identified as break points in the enthalpy-concentration curve; and (iv) increasing the hydrophilicity of the surfactant results in a decrease of the surfactant concentration producing the onset of solubilization.
Journal of Pharmaceutical Sciences 09/2005; 94(8):1747-55. · 3.06 Impact Factor
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ABSTRACT: The pharmacokinetics of pulmonary-administered sodium cromoglycate (SCG) has been studied in five healthy volunteers. SCG, 20 mg, was inhaled as a solution and encapsulated in dipalmitoyl phosphatidylcholine/cholesterol (1:1) liposomes. Liposomal SCG produced detectable drug levels in plasma from four volunteers taken 24 and 25 hr after inhalation. Inhaled SCG solution, although producing peak plasma levels more than sevenfold greater than liposomal drug, was not detectable in 24-hr samples from any volunteer. The decline in plasma levels following inhalation of liposomal SCG (reflecting the absorption phase) was best described by a biexponential equation. The two absorption rate constants differed by more than an order of magnitude. The rapid absorption phase was probably due to free or surface-adsorbed SCG in the liposomal formulation, since the absorption rate constant for this phase did not differ significantly from the absorption rate constant for SCG in solution. The phase of slow drug absorption may then be attributed to absorption of drug released from vesicles. The data indicate that encapsulation of SCG prior to pulmonary administration prolonged drug retention within the lungs and altered its pharmacokinetics.
Pharmaceutical Research 06/1989; 6(7):633-636. · 4.09 Impact Factor
