International Journal of Pharmaceutics (v.221, #1-2)
Biomedical applications of collagen by Chi H. Lee; Anuj Singla; Yugyung Lee (1-22).
Collagen is regarded as one of the most useful biomaterials. The excellent biocompatibility and safety due to its biological characteristics, such as biodegradability and weak antigenecity, made collagen the primary resource in medical applications. The main applications of collagen as drug delivery systems are collagen shields in ophthalmology, sponges for burns/wounds, mini-pellets and tablets for protein delivery, gel formulation in combination with liposomes for sustained drug delivery, as controlling material for transdermal delivery, and nanoparticles for gene delivery and basic matrices for cell culture systems. It was also used for tissue engineering including skin replacement, bone substitutes, and artificial blood vessels and valves. This article reviews biomedical applications of collagen including the collagen film, which we have developed as a matrix system for evaluation of tissue calcification and for the embedding of a single cell suspension for tumorigenic study. The advantages and disadvantages of each system are also discussed.
Keywords: Collagen; Biomaterial; Drug/protein/gene delivery; Tissue engineering;
Topical transfection using plasmid DNA in a water-in-oil nanoemulsion by Huailiang Wu; Chandrasekharan Ramachandran; Anna U Bielinska; Kristen Kingzett; Rong Sun; Norman D Weiner; Blake J Roessler (23-34).
Expression plasmids encoding chloramphenicol acetyltransferase (CAT) or human interferon-α2 cDNA were formulated in water-in-oil nanoemulsions and applied to murine skin. The histological location of transfected cells was assessed by in situ DNA PCR and showed that the deposition of plasmid DNA was primarily in follicular keratinocytes. Transgene expression in the skin was monitored for 24–72 h, following topical application of either single or multiple daily doses by quantitative RT-PCR and ELISA. It was found that transgene expression was optimal at 24 h following topical application of a single dose of water-in-oil nanoemulsion containing plasmid DNA. Dose–response studies using a total dose of 3, 10 or 30 μg of plasmid DNA suggested that topical transfection using nanoemulsions is subject to both threshold and saturation effects. None of the cationic liposome formulations tested as controls mediated transgenic protein expression at levels higher than background values of the ELISAs used to assay transgenic protein. Single and multiple dose experiments using human interferon-α2 as a transgene indicated that the efficiency of nanoemulsion mediated transfection was most effective in the context of normal versus atrophic hair follicles. In addition, the total amount of human interferon-α2 present in skin appeared to accumulate as a consequence of multiple dosing. Histologic evaluation of treated skin showed no overt signs of toxicity or irritation associated with the short-term application of the nanoemulsions. The results suggest that water-in-oil nanoemulsions can be used to facilitate transfection of follicular keratinocytes in vivo.
Keywords: Non-viral vectors; Water-in-oil nanoemulsions; In vivo transfection; Keratinocytes;
The Interaction between wheat germ agglutinin and other plant lectins with prostate cancer cells Du-145 by Franz Gabor; Ursula Klausegger; Michael Wirth (35-47).
The bioadhesive properties of fluorescein-labeled plant lectins with different carbohydrate specificities were investigated by flow cytometry at 4 and 37°C using Du-145 prostate cancer cells. At both temperatures the lectin association rate increased following the order: Dolichos biflorus agglutinin (DBA)<peanut agglutinin<Ulex europaeus isoagglutinin I<Lens culinaris agglutinin<Solanum tuberosum lectin≪wheat germ agglutinin (WGA), reflecting the glycosylation pattern of Du-145 cells. Both, the BSA-binding capacity of the cells referring to nonspecific binding and inhibition studies using the complementary carbohydrate, assured specificity of the lectin–cell interactions except for DBA. The WGA-association rate of Du-145 cells was dependent on temperature indicative for cellular uptake of membrane-bound WGA. Intracellular enrichment of WGA was confirmed by confocal microscopy. As resulted from experiments in presence of ouabain active transport mechanisms were involved in cellular uptake of WGA. Equilibration of the intracellular pH with monensin pointed to accumulation of intracellular located WGA within acidic compartments of Du-145 cells such as the lysosomes or the trans-Golgi complex. Consequently the interaction of WGA with Du-145 cells at 37°C is a one way process due to immediate active transport of membrane-bound lectin into acidic compartments of prostate cancer cells.
Keywords: Du-145; Lectin; Wheat germ agglutinin; Bioadhesion; Flow cytometry; Active transport;
The effects of packaging on the stability of a moisture sensitive compound by Jennifer G Allinson; Richard J Dansereau; Adel Sakr (49-56).
Packages that provided stability (less than a 10% loss in potency) of a moisture sensitive compound (PGE-7762928) in tablet form at accelerated conditions for 6 months were identified. The equilibrium moisture content of the tablets at 25°C/60%RH, 30°C/60%RH and 40°C/75%RH were 2.3, 2.4, and 2.9%, respectively. The tablet equilibrium moisture content, degradation rate of unpackaged product, and the moisture barrier properties of the packages were used to predict the stability of the packaged product. The physical and chemical stability (HPLC assay) of the products were measured after 2, 4, 6, 8, 12, and 24 weeks at ICH conditions. The Containers-Permeation1 of polyvinyl chloride blisters, cyclic olefin blisters, aclar blisters, cold-form aluminum blisters was 0.259, 0.040, 0.008 and 0.001 mg per blister per day, respectively. At 6 months at 40°C/75%RH, the percent active was 84% in polyvinyl chloride blisters, 91% in cyclic olefin blisters, 97% in aclar blisters, 100% in cold-form aluminum blisters and 99% in an high density polyethylene bottle with a foil induction seal. The stability results for the packaged product were fairly consistent with the predictions based on the moisture sensitivity of the product and the moisture barrier properties of the respective package. To gain a better prediction, the flux value determined by the Containers-Permeation procedure was adjusted for the internal moisture concentration of the blister.
Keywords: Package; Stability; Moisture sensitivity; Tablet; Container's permeation; Fick's law;
Surfactant, but not the size of solid lipid nanoparticles (SLN) influences viability and cytokine production of macrophages by N Schöler; C Olbrich; K Tabatt; R.H Müller; H Hahn; O Liesenfeld (57-67).
After intravenous (i.v.) injection, solid lipid nanoparticles (SLN) interact with mononuclear cells. Murine peritoneal macrophages were incubated with SLN formulations consisting of Dynasan 114 coated with different surfactants. The present study was performed to examine the impact of surfactants, which are important surface defining components of SLN, on viability and cytokine production by macrophages. Cytotoxicity, as assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test, was strongly influenced by the surfactant used being marked with cetylpyridinium chloride- (CPC-) coated SLN at a concentration of 0.001% and further increased at SLN concentrations of 0.01 and 0.1%. All other SLN formulations — containing Poloxamine 908 (P908), Poloxamer 407 (P407), Poloxamer 188 (P188), Solutol HS15 (HS15), Tween 80 (T80), Lipoid S75 (S75), sodium cholate (SC), or sodium dodecylsulfate (SDS) — when used at the same concentrations reduced cell viability only slightly. None of the SLN formulations tested induced cytokine production but a concentration-dependent decrease of IL-6 production was observed, which appeared to be associated with cytotoxic effects. IL-12 and TNF-α were detected neither in supernatants of macrophages treated with SLN at any concentration nor in those of untreated cells. In contrast to the type of surfactant, the size of SLN was found neither to affect cytotoxicity of SLN nor to result in induction or digression of cytokine production by macrophages. In conclusion, testing the effects of surfactants on SLN on activity of macrophages is a prerequisite prior to in vivo use of SLN.
Keywords: Solid lipid nanoparticles; Surfactant; Surface modification; Size; Peritoneal macrophages; Cytokines; Cytotoxicity;
Characterisation and disintegration properties of irradiated starch by M De Kerf; W Mondelaers; P Lahorte; C Vervaet; J.P Remon (69-76).
Irradiation treatment could provide a quick and simple way to modify the physical, chemical and pharmaceutical properties of biopolymers such as starch. Corn, potato and drum dried corn starch were exposed to X-ray and electron beam (e-beam) irradiation treatment at doses of 10, 50 and 100 kGy. The disintegration properties of these starches were compared using α-lactose monohydrate tablets containing 5% (w/w) starch as disintegrant. Starch solubility increased, while its swelling capacity decreased with increasing irradiation dose. The irradiation treatment caused fragmentation of the amylopectin fraction. Irradiation modified the different starches thoroughly, showing remarkable differences in disintegration properties after X-ray treatment and e-beam modification. The e-beam modification resulted in significantly higher disintegration times of the tablets.
Keywords: Disintegration; Starch; Irradiation; Starch characterisation; X-ray; Electron beam;
DC Calcium lactate, a new filler-binder for direct compaction of tablets by Gerad K Bolhuis; Anko C Eissens; Edzo Zoestbergen (77-86).
In this paper, a directly compressible form of calcium lactate is introduced as a filler-binder for direct compaction of tablets. Calcium lactate is one of the most important calcium sources and has, in comparison with other organic calcium salts, a good solubility and bioavailability. Two different modifications, calcium lactate trihydrate and calcium lactate pentahydrate are described in the main pharmacopoeias. This paper describes that the compaction properties of calcium lactate pentahydrate (Puracal® DC) are much better than those of the calcium lactate trihydrate (Puracal® TP). Calcium lactate pentahydrate has better compaction properties than dicalcium phosphate dihydrate, even if lubricated with magnesium stearate. Moreover, as a consequence of its crystalline structure, calcium lactate pentahydrate has a low compaction speed sensitivity. This means that, in combination with its excellent flow properties, calcium lactate pentahydrate is a suitable filler-binder in tablets prepared by high-speed compaction. In a number of formulation examples it will be illustrated that tablets containing calcium lactate pentahydrate as main or additional filler-binder have a short disintegration time and a fast drug release. Directly compressible calcium lactate can be considered as a promising excipient in both pharmaceutical tablets and tablets for the nutraceutical market.
Keywords: Tablet; Direct compaction; Filler-binder; Calcium lactate;
Development of a new system for prediction of drug absorption that takes into account drug dissolution and pH change in the gastro-intestinal tract by Michiya Kobayashi; Noriaki Sada; Mitsuru Sugawara; Ken Iseki; Katsumi Miyazaki (87-94).
A new system for prediction of drug absorption that takes into account drug dissolution and pH change in the gastro-intestinal tract was developed. In this new system, a drug (solid form) is added into a drug-dissolving vessel (pH 1.0) and the dissolved drug is transferred to a pH adjustment vessel (pH 6.0). Then the drug solution is transferred to the apical surface of Caco-2 cells, and the permeation rate of the drug across a Caco-2 monolayer is determined. This system was able to predict the oral absorption ratios of ten water-soluble drugs in humans. Using this system, it was predicted that drugs that permeated Caco-2 at a rate of more than 0.1% of the dose in 200 min would be almost completely absorbed after oral administration in humans. For a drug whose permeation ratio was less than 0.03%, the absorption ratio was predicted to be less than 30%. This system also enabled prediction of the absorption rate and variability in the absorption of albendazole, a drug with poor water solubility. It also enabled assessment of the improvement in absorption using a solid dispersion of albendazole-polymers that improved the water solubility. The results suggest that this system is useful for oral absorption screening of new drugs and pharmaceutical products.
Keywords: Intestinal absorption; Prediction; Caco-2; Human; Screening;
Membrane transport of hydrocortisone acetate from supersaturated solutions; the role of polymers by S.L Raghavan; B Kiepfer; A.F Davis; S.G Kazarian; J Hadgraft (95-105).
Permeation of hydrocortisone acetate (HA) from supersaturated solutions was studied across a model silicone membrane. Supersaturated solutions were prepared using the cosolvent technique with propylene glycol and water (or aqueous polymer solutions) as the cosolvents. In the absence of the polymer, the flux of HA was similar at all degrees of saturation and was not significantly different from the value obtained for a saturated solution. Flux enhancement, as a result of supersaturation, was observed with all the polymers. The flux increased with increasing polymer concentration, reached a maximum and decreased at higher polymer percentages. The amount of polymer required for maximum enhancement differed for each polymer. The decrease of flux at high polymer concentrations is attributed to changes in microviscosity and a marginal increase in solubility. The infrared spectroscopic and differential scanning calorimetry data suggest that HA–polymer interactions occurred through hydrogen bonding thus explaining the proposed mechanism of the anti-nucleant properties of the polymers.
Keywords: Supersaturation; Cosolvents; In vitro permeation; Hydrocortisone acetate; Antinucleant polymers; Silicone membrane; ATR-IR spectroscopy;
In vitro release of dexmedetomidine from silica xerogel monoliths: effect of sol-gel synthesis parameters by Pirjo Kortesuo; Manja Ahola; Minna Kangas; Antti Yli-Urpo; Juha Kiesvaara; Martti Marvola (107-114).
Dexmedetomidine, an alpha 2-agonist, was incorporated as a hydrochloride salt into silica xerogel in order to evaluate the effect of sol-gel synthesis parameters: pH of the sol, water/alkoxide molar ratio, drug concentration and size of the device on the drug release rate and degradation rate of the matrix. This study showed that diffusion controlled the release of dexmedetomidine from silica xerogel prepared between pH 1 and pH 5. The drug release was, however, slowest near the zero charge of silica xerogel (pH 2–3). The burst of dexmedetomidine, a lipophilic, but in the form of hydrochloride salt water-soluble drug, was increased from the matrix prepared either below or above the isoelectric point. It follows that the optimum pH for preparing a drug delivery device for dexmedetomidine, is near the zero charge of silica xerogel, where the degradation of the matrix was also slowest. In addition to processing pH, the release rate of drugs can be controlled by changing the water/alkoxide molar ratio of the sol.
Keywords: Silica xerogel; Drug delivery; Dexmedetomidine;
Flow injection potentiometric determination of bismuth(III) in anti-acid formulations by Marcos F.S Teixeira; Orlando Fatibello-Filho (115-121).
A flow injection potentiometric procedure is proposed for determining bismuth(III) in anti-acid formulations. In this work, a tubular electrode coated with an ion-pair formed between [Bi(EDTA)]− and tricaprylylmethylammonium cation (Aliquat 336) in a poly(vinylchloride) (PVC) was constructed and used in a single channel flow injection system. The effect of membrane composition, pH and flow injection parameter over the Bi(III) tubular electrode response (slope (mV/decade)) was initially evaluated in quintuplicate in 0.5 mol l−1 EDTA solution as carrier. The best response (−59.6±0.9 mV/decade) was attained with the 5% m/m ion-pair; 65% m/m o-nitrophenyl octyl ether (o-NPOE) and 30% m/m PVC in pH 6–9. The electrode showed a linear response to E (mV) versus log [Bi(EDTA)]− in the bismuth(III) concentration range from 2.0×10−5 to 1.0×10−2 mol l−1 and a useful lifetime of at least 5 months (more than 1000 determinations for each polymeric membrane). The detection limit was 1.2×10−5 mol l−1 and the R.S.D. was less than 2.0% for a solution containing 5.0×10−4 mol l−1 bismuth(III) (n=10). Several species such as Cd(II), Mn(II), Ni(II), Zn(II), Co(II), Cu(II), Mg(II), Cr(III) and Al(III) at 1.0×10−3 mol l−1 concentration in 0.5 mol l−1 EDTA solution did not cause any interference. The frequency rate was 90 determinations per hour and the results obtained for bismuth(III) in anti-acid formulations using this flow procedure and those obtained using a spectrophotometric procedure are in agreement at the 95% confidence level.
Keywords: Bismuth(III) tubular ion-selective electrode; Ethylenediamintetraacetate; Anti-acid formulations; Flow injection;
Thermoanalytical and spectroscopic characterisation of solid-state retinoic acid by V Berbenni; A Marini; G Bruni; A Cardini (123-141).
Thermoanalytical (differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), thermogravimetric analysis coupled with Fourier transform infrared spectroscopy (TG/FTIR)) and spectroscopic (X-ray diffraction (XRD), ultraviolet–visible (UV–Vis), mass spectrometry (MS) and Fourier transform infrared diffuse reflectance (DRIFT) measurements have been used to characterise solid-state retinoic acid (RA) from a chemico-physical point of view. Between 130 and 160°C, a phase transition takes place that does not correspond to the transition between the known monoclinic and triclinic phases (DSC and XRD evidence). By annealing in air (in the 130–160°C temperature range and for different times), an exothermic oxidative degradation occurs that, depending on the thermal treatment, competes with the mentioned phase transition (TGA evidence). Spectroscopic techniques (UV–Vis, MS and DRIFT) allow one to conclude that the new solid phase is still constituted by retinoic acid with a different orientation of the side chain. Finally, RA does not undergo stable melting: the fragmentation patterns, both in air and in nitrogen, have been examined by TG/FTIR.
Keywords: All-trans retinoic acid; Tretinoin; Solid-state characterisation; Phase transition;
Effect of dose on the biodistribution and pharmacokinetics of PLGA and PLGA–mPEG nanoparticles by Z Panagi; A Beletsi; Gregory Evangelatos; E Livaniou; D.S Ithakissios; K Avgoustakis (143-152).
The effect of nanoparticle dose on the biodistribution and pharmacokinetics of conventional PLGA and stealth poly(Lactide-co-glycolide)–monomethoxypoly(ethyleneglycol) (PLGA–mPEG) nanoparticles was investigated. The precipitation-solvent diffusion method was used to prepare PLGA and PLGA–mPEG nanoparticles labeled with 125I-cholesterylaniline. These were administered intravenously (i.v.) in mice and at predetermined time intervals the animals were sacrificed and their tissues were excised and assayed for radioactivity. Within the dose range applied in this study, blood clearance and mononuclear phagocyte system (MPS) uptake of the PLGA nanoparticles depended on dose whereas they were independent of dose in the case of the PLGA–mPEG nanoparticles. Increasing the dose, decreased the rates of blood clearance and MPS uptake of the PLGA nanoparticles, indicating a certain degree of MPS saturation at higher doses of PLGA nanoparticles. The dose affected the distribution of PLGA nanoparticles between blood and MPS (liver) but it did not affect the nanoparticle levels in the other tissues. Within the range of doses applied here, the PLGA nanoparticles followed non-linear and dose-dependent pharmacokinetics whereas the PLGA–mPEG nanoparticles followed linear and dose-independent pharmacokinetics. In addition to the prolonged blood residence, the dosage-independence of the pharmacokinetics of the PLGA–mPEG nanoparticles would provide further advantages for their application in controlled drug delivery and in drug targeting.
Keywords: poly(Lactide-co-glycolide); poly(Lactide-co-glycolide)-monomethoxy(polyethyleneglycol); Biodistribution; Pharmacokinetics; Effect of dose;
Release kinetics and immunogenicity of parvovirus microencapsulated in PLA/PLGA microspheres by Eszter Pálinkó-Biró; Gábor Rónaszèki; Hans P. Merkle; Bruno Gander (153-157).
The aim of this work was to examine the immunogenicity of microencapsulated inactivated duck parvovirus in Muscovy duck (Cairina moschata) and goose. Inactivated duck parvovirus suspension was microencapsulated into 14–17 kDa poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA50:50H) by coacervation. The in vitro antigen release from individual and mixed PLA and PLGA50:50H microspheres (MS) was biphasic with an initial lag-phase of approx. 10 days followed by a relatively constant release over additional 12 days. By varying the composition of PLA+PLGA50:50H MS mixtures from 3+1 to 1+3, the release kinetics could be altered and controlled efficiently. The antigen-loaded MS were injected subcutaneously into ducks. The immune response, expressed as virus neutralisation (VN) titres, after single administration of MS was modest, i.e. below 200 over the 6 weeks tested, unless the animals were pre-immunised 3 weeks before injecting the MS. The weak immune response was attributed to the low dose injected and inappropriate antigen release kinetics. With pre-immunised animals, however, the results were encouraging and showed that the encapsulated parvovirus was immunogenic.
Keywords: Duck parvovirus; Virus microencapsulation; Biodegradable microspheres; Virus neutralisation; Antigen delivery system;
Distributions of results of cetirizine dihydrochloride assay in bulk material by Alexander Weisman; Ilya Kuselman (159-163).
The distribution of the cetirizine dihydrochloride assay results in correlation with the pharmacopoeia limits is analyzed. The data for analysis were obtained at Chemagis Ltd., Israel, for 13 batches during a year in two laboratories by five analysts using three different titroprocessors (total 114 results of the determination). The hypothesis on the normal distribution of the data was tested using ω 2-criterion and accepted at the level of confidence 0.90. A control chart is designed for indication of warning and action limits of the determination results and for diagnoses of outliers in the further titrations. The distribution of the analyte content in different batches and the distributions of the titration results at the pharmacopoeia limits were plotted. The probabilities of the erroneous decisions of Type 1 and Type 2 on the batch quality were calculated from these distributions.
Keywords: Certirizine dihydrochloride; Assay; Distribution; Pharmacopoeia limits; Batch quality;
Characterisation of the aggregation behaviour in a salmeterol and fluticasone propionate inhalation aerosol system by Yonatan Michael; Martin J. Snowden; Babur Z. Chowdhry; Ian C. Ashurst; Craig J. Davies-Cutting; Trevor Riley (165-174).
The nature of the drug–drug aggregation phenomena between salmeterol xinafoate and fluticasone propionate used in a metered-dose inhaler system has been examined. Interactions between the drugs in the solvents 1,1,2-trichlorotrifloroethane (CFC-113) and 1,1,1,2-tetrafluoroethane (HFA-134a) have been characterised using a focused beam reflectance measurement probe by measuring the average floc size of the drug particles individually and in combination as a function of stirrer rate. The floc composition in the CFC-113 system, where the drug particles cream, was determined by high-performance liquid chromatography analysis. The aggregation behaviour of the individual drugs was shown to depend on the physical and chemical properties of both the drug substance and the media. Larger flocs were observed for salmeterol xinafoate compared with fluticasone propionate, while both drugs formed larger aggregates in HFA-134a compared with in CFC-113. The floc composition studies demonstrated that, in the combined formulation in CFC-113, salmeterol xinafoate and fluticasone propionate aggregate together to form hetero-flocs. The interaction between the two drugs was such that they did not separate on creaming, despite having different densities. The average floc size of the combined drug suspension was also found to depend on the dispersion medium.
Keywords: Salmeterol xinafoate; Fluticasone propionate; HFA-134a; CFC-113; Aggregation; Focused beam reflectance;
Production of anti-CD3 and anti-CD7 ricin A-immunotoxins for a clinical pilot study by Ypke V.J.M. van Oosterhout; J.Liesbeth van Emst; Hans H. Bakker; Frank W.M.B. Preijers; Anton V.M.B. Schattenberg; Dirk J. Ruiter; Sabine Evers; Joop P. Koopman; Theo de Witte (175-186).
This report describes the preparation of an immunotoxin-combination, consisting of an anti-CD3 and anti-CD7 monoclonal antibody (MoAb) both conjugated to the A-chain of plant toxin ricin, for the experimental treatment of graft-versus-host disease. MoAbs and toxin were conjugated by conventional biochemical and chromatographic techniques. Raw materials, intermediate and final products were evaluated in accordance with the relevant ‘points to consider’ of the FDA. Yields, purity and sterility of the two final products were all satisfactory. Preservation of MoAb-affinity and toxin-activity were confirmed in biological assays. The LD50, 25–45 mg immunotoxin-combination/kg mouse, equalled that of similar immunotoxins already in clinical use. Because in vitro cross-reactivity screening revealed an unexpected binding of the CD3-MoAb to the esophagus epithelium, human doses of immunotoxin-combination were administered to two cynomolgus monkeys. Clinically relevant serum concentrations were obtained without irreversible toxicities occurring. The T 1/2 varied between ∼6 and 9 h and the C max ranged from 1.8 to 3.9 μg/ml. The main side effect was a transient rise of serum creatine kinase. Importantly, neither damage nor binding of the CD3-immunotoxin to the monkey esophagus epithelium could be demonstrated. It was concluded that sufficient material of proper quality and with an acceptable toxicity profile was produced, warranting the evaluation in a clinical pilot-study.
Keywords: Immunotoxin; Quality control; Antigens CD3 & CD7; Mice BALB/C; Cynomolgus monkey; Ricin;
Rheological properties of creams with four different surfactant combinations - effect of storage time and conditions by Mirka Korhonen; Leena Hellen; Jouni Hirvonen; Jouko Yliruusi (187-196).
Changes in the rheological properties of four o/w cream formulations differing in the combination of surfactants were studied. The non-ionic surfactants used were soybean derivatives, polyethylene glycol 10 and 25 soya sterol, and sorbitol derivatives, sorbitan monooleate and trioleate. Combinations of the soybean and sorbitol derivatives were used. The rheological properties were tested during a 28-day storage period at three different storage conditions (cold, room temperature and accelerated conditions). In addition to dynamic and static rheological tests, droplet size distributions and conductivities of the creams were also determined. The consistency of the creams containing polyethylene glycol 10 soya sterol decreased during storage. Despite the greatest decreases in consistency, the creams containing polyethylene glycol 10 soya sterol exhibited the most viscoelastic structures with linear viscoelastic behaviour. Storing the creams for 28 days in the three different storage conditions made the differences in the consistency of the formulations smaller. All three storage conditions were involved when the conditions of the most viscoelastic cream of each formulation was specified. In the case of linearly viscoelastically behaving creams containing polyethylene glycol 10 soya sterol, all the rheological tests correlated with the droplet size distributions and the conductivity tests.
Keywords: Dynamic rheological tests; Rheology of creams; Static rheologicl tests; Storage conditions; Storage time; Surfactants;
The influence of incubation temperature and surfactant concentration on the interaction between dimyristoylphosphatidylcholine liposomes and poloxamer surfactants by Jonathan D Castile; Kevin M.G Taylor; Graham Buckton (197-209).
Differential scanning calorimetry and photon correlation spectroscopy have been used to study the interaction between poloxamers P338 and P407 and dimyristoylphosphatidylcholine (DMPC) liposomes. The extent of the interaction was found to be dependent on the incubation temperature in addition to the poloxamer concentration. At low poloxamer concentrations (0.1–1.0% w/v) an interaction with the phospholipid bilayer was detected by a reduction of the pre-transition enthalpy of DMPC. At higher concentrations (2.0–5.0% w/v), the main phase transition temperature of the liposomes decreased and the endotherm broadened with a shoulder on the high temperature side, indicative of phase separation. Maximum increases in the diameter of small freeze–thaw extruded liposomes were shown to occur at temperatures close to the poloxamer critical micelle temperatures. At higher temperatures and surfactant concentrations there was evidence of solubilization of phospholipid into mixed micelles.
Keywords: Differential scanning calorimetry; Liposome; Micelle; Phase transition temperature; Phospholipid; Poloxamer; Surfactant;
The dispersive component of the surface free energy of powders assessed using inverse gas chromatography and contact angle measurements by Odon Planinšek; Andrijana Trojak; Stane Srčič (211-217).
The nonpolar parameter of solid surface free energy γ s d has been determined for some pharmaceutical powders by means of contact angle measurement (Wilhelmy plate method) and inverse phase gas chromatography (IGC). For most samples, a good correlation between the results of the two methods was found. Additionally it was found that to get comparable results with the IGC method, contact angles obtained with totally nonpolar liquid should be used for calculating γ s d. Comparison of our results with those from the literature showed that the correlation depends on the method used for contact angle determination and the properties of the liquids used for contact angle measurements.
Keywords: Contact angle; Wilhelmy plate method; Inverse gas chromatography; Surface free energy;
Solubility of drugs in the presence of gelatin: effect of drug lipophilicity and degree of ionization by Paraskevi Kallinteri; Sophia G. Antimisiaris (219-226).
The solubility of seven drugs (nitrofurantoin, chlorothiazide, phenobarbital, prednisolone, griseofulvin, diazepam and piroxicam) in the absence and presence of gelatin was measured, at three different pH values (3.7, 5.0 and 7.0) at 37°C. Drugs studied had different physicochemical properties (log P, pK a, aqueous solubility) and their solubility in presence of 0.1 and 0.5% (w/v) hydrolyzed (and in some cases common) gelatin was estimated. Results show that the solubility of all drugs is significantly enhanced, especially in the presence of 0.5% gelatin. This gelatin-induced enhancement in drug solubility is higher in the pH in which acidic drugs are less ionized, especially for the less lipophilic acidic drugs (nitrofurantoin, chlorothiazide). In all cases, drug solubility in presence of gelatin is correlated with their aqueous solubility. Therefore, the established relationships between aqueous and gelatin solubility can be employed to derive an estimate of the drug solubility in presence of gelatin once its aqueous solubility is known. With the exception of piroxicam which is highly ionized and phenobarbital which is relatively soluble, there seems to be a tendency for larger gelatin-induced increases in solubility as drug lipophilicity increases or aqueous solubility decreases.
Keywords: Solubility; Gelatin; Hydrolyzed gelatin; Drugs;
Intranasal delivery of tenoxicam in rat by C.Vijaya Raghavan; V.D Abimon (227-229).
Intranasal delivery of tenoxicam was studied in male rats on single dose administration of 0.36 mg/rat and compared with intravenous administration. Tenoxicam plasma levels were determined by RP-HPLC method with UV detection that employed piroxicam as an electroactive internal standard in the analysis. Following intravenous administration the area under the plasma concentration curve was 2452.17±86.49 ng h/ml as compared to 1357.69±102.36 ng h/ml following intranasal dosing. This corresponds to a relative bioavailability of 55.36%.
Keywords: Tenoxicam; Nasal delivery; Bioavailability study; Rat;
Erratum to “The effect of pore formers on the controlled release of cefadroxil from a polyurethane matrix” by Ji-Eon Kim; Seung-Ryul Kim; Sun-Hee Lee; Chi-Ho Lee; Dae-Duk Kim (231).
Notice board (233-236).