1.
Haupt, Dan, et al.
(författare)
Medication persistence among patients with asthma/COPD drugs
2008
Ingår i: Pharmacy World & Science. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 30:5, s. 509-514
Tidskriftsartikel (refereegranskat) abstract
OBJECTIVE: To determine medication possession ratio (MPR) of patients with asthma/COPD drugs. METHOD: Individual patient's volumes of asthma/COPD drugs (ATC-code R03) for 2000-2004 were obtained from a pharmacy record database. For each patient the MPR was calculated as the percentage of the treatment time that the patient had drugs available. MAIN OUTCOME MEASURE: Medication possession ratio (MPR). RESULTS: A total of 1,812 patients, 20 years and older, with dispensed asthma/COPD drugs were registered in the database, 928 patients (51%) had acquired drugs less than once per year (68% for 20-29 years old) during the 5-year study. Only 13% of the patients had steroids and steroid combinations available to allow continuous treatment. Eight percent of the patients 20-29 years old had MPR > or = 80% of all the included drugs and 5% when only steroids and steroid combinations were considered. About 25% of the patients had acquired 80% of the total volume of asthma/COPD drugs. CONCLUSION: The majority of the patients, and particularly those in the youngest age group used asthma/COPD drugs only sporadically. This may indicate undermedication which is likely to have a negative impact on patient outcome.
2.
3.
Toropainen, Tarja, et al.
(författare)
Crystal structure changes of gamma-cyclodextrin after the SEDS process in supercritical carbon dioxide affect the dissolution rate of complexed budesonide
2007
Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 24:6, s. 1058-1066
Tidskriftsartikel (refereegranskat) abstract
Purpose. The present study describes the crystal structure changes of γ-cyclodextrin (γ-CD) during the solution enhanced dispersion by supercritical fluids (SEDS) process and its effect on dissolution behaviour of complexed budesonide. Materials and Methods. γ-CD solution (10 mg/ml in 50% ethanol) was pumped together with supercritical carbon dioxide through a coaxial nozzle with or without a model drug, budesonide (3.3 mg/ml). The processing conditions were 100 b and 40, 60 or 80°C. γ-CD powders were characterised before and after vacuum-drying (2-3 days at RT) with XRPD, SEM and NMR. Budesonide/γ-CD complexation was confirmed with DSC and XRPD. The dissolution behaviour of complexed budesonide was determined in aqueous solution (1% γ-CD, 37°C, 100 rpm). Results. During the SEDS process (100 b, 40 and 60°C), γ-CD and budesonide/γ-CD complexes crystallized in a tetragonal channel-type form. The vacuum-drying transformed crystalline γ-CD into amorphous form while the complexes underwent a tetragonal-to-hexagonal phase transition. The increase in the processing temperature decreased the crystallinity of γ-CD. At 80°C, amorphous γ-CD was obtained while the complexes crystallized in a hexagonal channel-type form. The dissolution behaviour of budesonide/γ-CD complexes was dependent on their crystal structure: the tetragonal form dissolved faster than the hexagonal form. Conclusions. The crystal structure of γ-CD and subsequently, the dissolution rate of complexed budesonide, can be modified with the processing conditions.
4.
Toropainen, Tarja, et al.
(författare)
Preparation of budesonide/gamma-cyclodextrin complexes in supercritical fluids with a novel SEDS method
2006
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 95:10, s. 2235-2245
Tidskriftsartikel (refereegranskat) abstract
The aim was to investigate if solid drug/cyclodextrin complexes could be produced in a single-step process with a solution enhanced dispersion by supercritical fluids (SEDS) method. Budesonide and gamma-cyclodextrin (CD) solutions (50% or 99.5% ethanol) were pumped from the same (conventional method) or separate (modified method) containers together with supercritical carbon dioxide through a coaxial nozzle into a particle formation chamber. The pressure was maintained at 100, 150 or 200 bar with a temperature of 40, 60 or 80 degrees C. SEDS-processed powders were characterised with HPLC, DSC and XRPD for budesonide content, complexation and crystallinity. The budesonide dissolution rate was determined in 1% gamma-CD aqueous solution. Solid, white budesonide/gamma-CD complex particles were formed using the conventional and modified SEDS processes. The complexation efficiency was dependent on the processing conditions. For example, with the conventional method (100 bar, 60 C) the yield of the powder was 65 +/- 12% with 0.14 +/- 0.02 mg budesonide/mg powder, corresponding to 1:2 drug:CD molar ratio. The dissolution rate of this complexed budesonide (93 +/- 2% after 15 min) was markedly higher compared to unprocessed micronised budesonide (41 +/- 10%) and SEDS-processed budesonide without CD (61 +/- 3%). As a conclusion, SEDS is a novel method to produce solid drug/CD complexes in a single-step process.
5.
Velaga, Sitaram
(författare)
Preparation of Pharmaceutical Powders using Supercritical Fluid Technology : Pharmaceutical Applications and Physicochemical Characterisation of Powders
2004
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
The main aim of the thesis was to explore the potential of supercritical fluid (SF) techniques in the field of drug delivery. In particular, the relatively recently developed solution-enhanced dispersion by supercritical fluids (SEDS) technology has been employed in the preparation of particles/powders. The manufacturing, stability and bioavailability of a dosage form strongly depend on the physicochemical properties of the formulation particles. For example, dry powder inhalation (DPI) for administering drugs to the respiratory tract require particles in a narrow size range (1-5 μm) to be effective. The identification of polymorphs and control of purity are also important issues since the physicochemical properties and therapeutic effects of the alternative forms of a drug may differ substantially. Solvent-based traditional crystallisation processes provide the product that may require further down-stream processing to obtain particles for advanced drug delivery applications. This can result in unwanted changes in the physicochemical properties of the particles and thus affect the performance of the dosage form. SF processing has addressed many of the challenges in particle formation research. Among several SF technologies developed for particle processing over the last decade, the SEDS process with its specially designed co-axial nozzle with mixing chamber has resulted in improved control over the particle formation process. Carbon dioxide (CO2) was used as the SF, because it has low critical points and is non-toxic, non-flammable and relatively inexpensive. The initial part of the thesis concerns the formation of particles of model drugs such as hydrocortisone, budesonide and flunisolide using SEDS technology and the determination of the influence of processing conditions and solvents on particle characteristics such as size, shape and crystal structure. Particles of model drugs of differing shapes in a size range suitable for inhalation delivery were prepared. In the process, two new polymorphic forms of flunisolide were identified. This was the first report of SEDS technology being shown as a polymorph-screening tool. The remainder of the thesis deals with the development of SEDS technology for precipitating therapeutic proteins such as recombinant human growth hormone (hGH) from aqueous solutions. Powders of hGH were precipitated using SEDS without significant changes in the chemical or physical stability of the protein. The addition of sucrose to hGH in the feed solution promoted precipitation and minimised the detrimental effects of the solvent and/or the process on the physical aggregation of the protein. In conclusion, this thesis highlights the applicability of the SEDS process in drug delivery research and advances general understanding of the particle formation phenomenon. The SEDS process may also prove to be a potential alternative technology for the precipitation of stable powders of therapeutic proteins.
