Kenneth Ekman

Improved stability and release control of levodopa and metaraminol using ion-exchange fibers and transdermal iontophoresis

Achievement of controlled drug delivery and stability of drugs during storage is a problem also in transdermal drug delivery. The objective of this study was to determine, whether an easily oxidized drug, levodopa, could be stabilized during storage using pH-adjustment and ion-exchange fibers. Controlled transdermal delivery of the zwitterionic levodopa was attempted by iontophoresis and ion-exchange fiber. Ion-exchange kinetics and transdermal permeation of a cationic (presumably more stable) model drug, metaraminol, were compared to the corresponding data of levodopa. Levodopa was rapidly oxidized in the presence of water, especially at basic pH-values. At acidic pH-values the stability was improved significantly. Ion-exchange group and the pH had a clear effect on the release of both the levodopa and metaraminol from the ion-exchange fiber. The adsorption/release kinetics of metaraminol were more easily controllable than the corresponding rate and extent of levodopa adsorption/release. Iontophoretic enhancement of drug permeation across the skin was clearly more significant with the positively charged metaraminol than with the zwitterionic levodopa. Ion-exchange fibers provide a promising alternative to control drug delivery and to store drugs that are degraded easily.

Preparation of poly[ethylene-g-(vinylbenzyl chloride)] and functionalization with bis(phosphonic acid) derivatives

Abstract Poly[ethylene- g -(vinylbenzyl chloride)] ( 1 ) film was prepared and used as an intermediate for the synthesis of polymer supported bis(phosphonic acid) derivatives. ( 1 ) was synthesized by preirradiation grafting of vinylbenzyl chloride (VBC) on polyethylene film. A reaction time of 29 h gave ( 1 ) with a chlorine capacity of 4.7 mmol Cl/g. As shown by energy dispersive X-ray analysis, the depth of the graft modification can be varied from surface to bulk modification by controlling the reaction time. The gel content of the film was found to increase with increased extent of grafting. A 28% VBC grafted film was found to have a gel content of 91%. The swelling of the Poly[ethylene- g -(vinylbenzyl chloride)] ( 1 ) film in toluene or THF was rapid A 145% VBC grafted film swells 260 area % within 2 min in refluxing toluene. Tetraisopropyl methylene-bisphosphonate ( 2 ) or tetraethyl ethane-1,1-bisphosphonate ( 3 ) were reacted with NaH and used for nucleophilic substitution of chlorine in the poly[ethylene- g -(vinylbenzyl chloride)] film. Forty-six percent of the chlorine groups were substituted within 24 h using the sodium salt of tetraisopropyl methylenebisphosphonate ( 2 ) in a 10-fold excess in refluxing toluene. Under the same reaction conditions, using the sodium salt of tetraethyl ethane-1,1-bisphosphonate ( 3 ) gave 50% substitution. Energy dispersive X-ray analysis showed that the substitution reaction proceeds throughout the film at the same rate, which implies that the reaction is not mass-transfer controlled. Hydrolysis of the polymer supported bisphosphonate in hydrochloric acid to yield the bis(phosphonic acid) form gave a film which swells 60 area % in water at room temperature and 100 area % at 100°C.

The influence of EB‐crosslinking on barrier properties of HDPE–mica composites

High-density polyethylene (HDPE) was compounded with untreated and surface-treated mica (10, 20, 40 wt %) and composites were injection-molded. The composites were radiation crosslinked (100, 300, 700 kGy) and hydrocarbon permeability, tensile impact strength, and tensile strength at 25 and 80°C of the composites were examined. The permeability of HDPE decreased from 7 to 3.6 g/(d X m 2 ) by compounding the polymer with 20 wt % mica, and the permeability was additionally reduced to 1.3 g/(d X m 2 ) by irradiation of the compounds (700 kGy). When surface-treated mica was used, the permeability of the composite furthermore decreased to about 1.0 g/(d X m 2 ). Upon irradiation, the E modulus measured at 25°C increased 5% when the dose was 300 kGy. At 80°C, the corresponding increase was 40%. The tensile impact strength of an unfilled polymer increased more than three times by an irradiation dose of 700 kGy, and for a polymer with 10 wt % mica, the tensile impact strength was twice the level of an unirradiated composite.

Glass-ionomer cements based on poly(acrylic acid-co-vinyl alcohol) in drug release model formulations

The release of methylene blue from glass-ionomer cements based on a commercial glass powder and partly hydrolysed poly(acrylic acid-co-vinyl alcohol) has been studied. A series of random copolymers were synthesized from acrylic acid and vinyl acetate monomers, using feed ratios of 10-90 mol% acrylic acid. The acetate group was hydrolysed using sodium hydroxide. According to proton nuclear magnetic resonance analysis, the degree of hydrolysis was about 40%. The residual Na+ content in the samples after hydrolysis was in the vicinity of 3 mmol g-1 polymeric sample. The viscosity average molecular weight of the copolymers was the region of 60,000 g mol-1 for samples with low acrylic acid content and in the region of 300,000 g mol-1 for samples with a larger fraction of acrylic acid. Cement sample discs were prepared and the porosity of the cement was determined using N2 adsorption-desorption isotherms. The specific surface area was 10 m2 g-1, and the volume of the pores (< 20 nm) 0.035 cm3 g-1. The swelling indices and the release rates in two different buffers, pH 2.0 and pH 7.4, were determined for fresh and dried samples. An acidic environment did not bring about significant swelling in the samples and release of the model agent at pH 2.0 was limited. At a physiological pH value the cements swelled in a hydrogel manner and the fractional release of model agent increased.

Radiation stability of in situ stabilized polypropylene

Abstract The radiation stability upon exposure to high-energy radiation of different bi- and terpolymers such as poly[propylene- co -4-(hept-6-enyl)-2,6-di-tert-butylphenol], poly(propylene- co -6-phenylhex-1-ene) and poly[propylene- co -4-(hept-6-enyl)-2,6-di-tert-butylphenol- co -4-(hex-5- enyl)-2,2,6,6-tetramethylpiperidine] was studied. The films were exposed to a radiation dose of 25 kGy. The extent of radiation-induced degradation of the samples was determined by size exclusion chromatography. The most stable polymers found were a copolymer containing 0.82 wt% of 4-(hept-6-enyl)-2,6-di-tert-butylphenol and a commercial radiation-resistant polypropylene. The copolymers containing chemically bound hindered phenol moieties exhibited better protective properties than polypropylene reference samples containing the same concentration of admixed 3-(3,5-di-tert-butyl-4-hydroxylphenyl)propionate (Irganox 1010). The copolymers containing 6-phenylhex-1-ene or admixed phenyl decane showed reasonably good stability against radiation, whereas the formulations containing hindered amine light stabilizers showed relatively poor radiation stability.