Browsing by Subject "DOSAGE FORMS"

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  • Rautamo, Maria M; Kvarnström, Kirsi; Siven, Mia; Airaksinen, Marja; Lahdenne, Pekka Olavi; Sandler, Niklas (2020)
    Oral drug administration to pediatric patients is characterized by a lack of age-appropriate drug products and the off-label use of medicines. However, drug administration practices at hospital wards is a scarcely studied subject. The aim of this study was to explore the oral drug administration practices at pediatric hospital wards, with a focus on experiences and challenges faced, methods used to mitigate existing problems, drug manipulation habits, perceptions about oral dosage forms and future needs of oral dosage forms for children. This was a qualitative study consisting of focus group discussions with physicians, nurses and clinical pharmacists in a tertiary university hospital with the objective of bringing forward a holistic view on this research topic. These healthcare professionals recognized different administration challenges that were classified as either dosage form-related or patient-related ones. A lack of depot formulations developed especially for children as well as oral pediatric dosage forms of drug substances currently available as intravenous dosage forms was recognized. The preferred oral dosage forms were oral liquids and orodispersible tablets. Patient-centered drug administration practices including factors facilitating drug administration both at hospital wards and at home after patient discharge were identified. Among all healthcare professionals, the efficient cooperation in drug prescribing and administration as well as in educating the child's caregivers in correct administration techniques before discharge and improving the overall discharge process of patients was emphasized. This study complements the prevalent understanding that new dosage forms for children of varying ages and stages of development are still needed. It also brings a holistic view on different aspects of oral drug administration to pediatric patients and overall patient-centered drug administration practices.
  • Poller, Bettina; Strachan, Clare; Broadbent, Roland; Walker, Greg F. (2017)
    The purpose of this study was to evaluate electrospun drug loaded nanofibers as a new matrix for mini tablets. Prednisone, a poorly water-soluble drug, was loaded into povidone (polyvinylpyrrolidone, PVP) nanofibers using the process of electrospinning. The drug-loaded nanofiber mat was compressed into minitablets with a 2 mm diameter and a height of 2.63 0.04 mm. SEM analysis of the minitablet identified a nano-web structure with a nanofiber diameter in the range of 400-500 nm. The minitablets met the requirements of the US Pharmacopeia with respect to content uniformity and friability. DSC and XRPD analysis of the minitablet indicated that the drug-polymer mixture was a one-phase amorphous system. XRPD analysis of the drug loaded nanofiber mat after 10-months of storage at ambient temperature showed no evidence of recrystallization of the drug. Solubility and dissolution properties of the drug formulated into a nanofiber mat and minitablet were evaluated. These results show that electrospun nanofibers may provide a useful matrix for the further development of minitablets. (C) 2017 Elsevier B.V. All rights reserved.
  • Rautamo, Maria M; Kvarnström, Kirsi; Siven, Mia; Airaksinen, Marja; Lahdenne, Pekka Olavi; Sandler, Niklas (2020)
    The utilization of three-dimensional (3D) printing technologies as innovative manufacturing methods for drug products has recently gained growing interest. From a technological viewpoint, proof-of-concept on the performance of different printing methods already exist, followed by visions about future applications in hospital or community pharmacies. The main objective of this study was to investigate the perceptions of healthcare professionals in a tertiary university hospital about oral 3D-printed medicines for pediatric patients by means of focus group discussions. In general, the healthcare professionals considered many positive aspects and opportunities in 3D printing of pharmaceuticals. A precise dose as well as personalized doses and dosage forms were some of the advantages mentioned by the participants. Especially in cases of polypharmacy, incorporating several drug substances into one product to produce a polypill, personalized regarding both the combination of drug substances and the doses, would benefit drug treatments of several medical conditions and would improve adherence to medications. In addition to the positive aspects, concerns and prerequisites for the adoption of 3D printing technologies at hospital settings were also expressed. These perspectives are suggested by the authors to be focus points for future research on personalized 3D-printed drug products.
  • Rautaniemi, Kaisa; Vuorimaa-Laukkanen, Elina; Strachan, Clare J.; Laaksonen, Timo (2018)
    Pharmaceutical scientists are increasingly interested in amorphous drug formulations especially because of their higher dissolution rates. Consequently, the thorough characterization and analysis of these formulations are becoming more and more important for the pharmaceutical industry. Here, fluorescence lifetime-imaging microscopy (FLIM) was used to monitor the crystallization of an amorphous pharmaceutical compound, indomethacin. Initially, we identified different solid indomethacin forms, amorphous and gamma- and alpha-crystalline, on the basis of their time-resolved fluorescence. All of the studied indomethacin forms showed biexponential decays with characteristic fluorescence lifetimes and amplitudes. Using this information, the crystallization of amorphous indomethacin upon storage in 60 degrees C was monitored for 10 days with FLIM. The progress of crystallization was detected as lifetime changes both in the FLIM images and in the fluorescence-decay curves extracted from the images. The fluorescence-lifetime amplitudes were used for quantitative analysis of the crystallization process. We also demonstrated that the fluorescence-lifetime distribution of the sample changed during crystallization, and when the sample was not moved between measuring times, the lifetime distribution could also be used for the analysis of the reaction kinetics. Our results clearly show that FLIM is a sensitive and nondestructive method for monitoring solid-state transformations on the surfaces of fluorescent samples.
  • Pessi, Jenni; Svanbäck, Sami; Lassila, Ilkka; Haeggstrom, Edward; Yliruusi, Jouko (2017)
    We introduce a system with a lyophilic matrix to aid dissolution studies of powders and particulate systems. This lyophilic matrix method (LM method) is based on the ability to discriminate between non-dissolved particles and the dissolved species. In the LM method the test substance is embedded in a thin lyophilic core-shell matrix. This permits rapid contact with the dissolution medium while minimizing dispersion of non-dissolved particles without presenting a substantial diffusion barrier. The method produces realistic dissolution and release results for particulate systems, especially those featuring nanoscale particles. By minimizing method-induced effects on the dissolution profile of nanopowders, the LM method overcomes shortcomings associated with current dissolution tests. (C) 2017 Elsevier B.V. All rights reserved.
  • Semjonov, Kristian; Lust, Andres; Kogermann, Karin; Laidmäe, Ivo; Maunu, Sirkka Liisa; Hirvonen, Sami-Pekka; Yliruusi, Jouko; Nurk, Gunnar; Lust, Enn; Heinamäki, Jyrki (2018)
    The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus (R) (SOL) were prepared at a 1:3 drug-polymer weight ratio. Water was used as an external plasticizer to regulate a MES processing temperature and to improve fiber formation. The fiber size, surface morphology, physical solid state, drug-polymer (carrier) interactions, thermal and chemical stability and dissolution behavior of MSFs were investigated. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to measure T1(H-1), and the domain size of IND in MSFs (25-100 nm) was calculated from these results. Solid-state and thermal analysis confirmed the presence of amorphous solid dispersions of IND and SOL. IND was found to be chemically stable during an entire MES process. Only small drug content variability of different MSF batches was detected with high performace liquid chromatography (HPLC). Given findings were verified with the liquid NMR spectroscopy. The dissolution of MSFs was significantly faster than that of physical mixtures (PMs) or pure drug. The enhanced dissolution of MSFs was caused by high surface area, amorphous state of the drug and solubilizing properties of the carrier polymer (SOL).
  • Auvinen, Vili-Veli; Virtanen, Juhani; Merivaara, Arto; Virtanen, Valtteri; Laurén, Patrick; Tuukkanen, Sampo; Laaksonen, Timo (2020)
    Nanocellulose hydrogel has been shown to be an excellent platform for drug delivery and it has been lately studied as an injectable drug carrier. 3D printing is an effective method for fast prototyping of pharmaceutical devices with unique shape and cavities enabling new types of controlled release. In this study, we combined the versatility of 3D printing capsules with controlled geometry and the drug release properties of nanocellulose hydrogel to accurately modulate its drug release properties. We first manufactured non-active capsules via 3D printing from biocompatible poly(lactic acid) (PLA) that limit the direction of drug diffusion. As a novel method, the capsules were filled with a drug dispersion composed of model compounds and anionic cellulose nanofiber (CNF) hydrogel. The main benefit of this device is that the release of any CNF-compatible drug can be modulated simply by modulating the inner geometry of the PLA capsule. In the study we optimized the size and shape of the capsules inner cavity and performed drug release tests with common beta blockers metoprolol and nadolol as the model compounds. The results demonstrate that the sustained release profiles provided by the CNF matrix can be accurately modulated via adjusting the geometry of the 3D printed PLA capsule, resulting in adjustable sustained release for the model compounds.
  • Oblom, Heidi; Sjöholm, Erica; Rautamo, Maria; Sandler, Niklas (2019)
    To date, the lack of age-appropriate medicines for many indications results in dose manipulation of commercially available dosage forms, commonly resulting in inaccurate doses. Various printing technologies have recently been explored in the pharmaceutical field due to the flexible and precise nature of the techniques. The aim of this study was, therefore, to compare the currently used method to produce patient-tailored warfarin doses at HUS Pharmacy in Finland with two innovative printing techniques. Dosage forms of various strengths (0.1, 0.5, 1, and 2 mg) were prepared utilizing semisolid extrusion 3D printing, inkjet printing and the established compounding procedure for oral powders in unit dose sachets (OPSs). Orodispersible films (ODFs) drug-loaded with warfarin were prepared by means of printing using hydroxypropylcellulose as a film-forming agent. The OPSs consisted of commercially available warfarin tablets and lactose monohydrate as a filler. The ODFs resulted in thin and flexible films showing acceptable ODF properties. Moreover, the printed ODFs displayed improved drug content compared to the established OPSs. All dosage forms were found to be stable over the one-month stability study and suitable for administration through a naso-gastric tube, thus, enabling administration to all possible patient groups in a hospital ward. This work demonstrates the potential of utilizing printing technologies for the production of on-demand patient-specific doses and further discusses the advantages and limitations of each method.
  • Novakovic, Dunja; Isomäki, Antti; Pleunis, Bibi; Fraser-Miller, Sara J.; Peltonen, Leena Johanna; Laaksonen, Timo; Strachan, Clare Joanna (2018)
    The tendency for crystallization during storage and administration is the most considerable hurdle for poorly water-soluble drugs formulated in the amorphous form. There is a need to better detect often subtle and complex surface crystallization phenomena and understand their influence on the critical quality attribute of dissolution. In this study, the interplay between surface crystallization of the amorphous form during storage and dissolution testing, and its influence on dissolution behavior, is analyzed for the first time with multimodal nonlinear optical imaging (coherent anti-Stokes Raman scattering (CARS) and sum frequency generation (SFG)). Complementary analyses are provided with scanning electron microscopy, X-ray diffraction and infrared and Raman spectroscopies. Amorphous indomethacin tablets were prepared and subjected to two different storage conditions (30 °C/23% RH and 30 °C/75% RH) for various durations and then dissolution testing using a channel flow-through device. Trace levels of surface crystallinity previously imaged with nonlinear optics after 1 or 2 days of storage did not significantly decrease dissolution and supersaturation compared to the freshly prepared amorphous tablets while more extensive crystallization after longer storage times did. Multimodal nonlinear optical imaging of the tablet surfaces after 15 min of dissolution revealed complex crystallization behavior that was affected by both storage condition and time, with up to four crystalline polymorphs simultaneously observed. In addition to the well-known α- and γ-forms, the less reported metastable ε- and η-forms were also observed, with the ε-form being widely observed in samples that had retained significant surface amorphousness during storage. This form was also prepared in the pure form and further characterized. Overall, this study demonstrates the potential value of nonlinear optical imaging, together with more established solid-state analysis methods, to understand complex surface crystallization behavior and its influence on drug dissolution during the development of amorphous drugs and dosage forms.