Hypromellose, a semi-synthetic derivative of cellulose, is by far the most commonly used hydrophilic polymer for the development of oral controlled release dosage forms. Modulation of drug release can be achieved by combination of different viscosity grades of hypromellose or combination with other polymers including water insoluble, non-ionic or ionic polymers. These combinations of excipients are widely used in the formulation of standard and also modern dosage forms including matrix tablets, multilayer tablets, minitablets, floating gastroretentive system, mucoadhesive dosage forms, micro- and nanoparticles, 3D printed dosage forms, and nanofiber-based drug delivery systems.
- MeSH
- deriváty hypromelózy * chemie farmakokinetika MeSH
- farmaceutická chemie MeSH
- farmaceutické pomocné látky chemie farmakokinetika MeSH
- léky s prodlouženým účinkem chemická syntéza chemie farmakokinetika MeSH
- tablety chemie farmakokinetika MeSH
- uvolňování léčiv MeSH
- Publikační typ
- práce podpořená grantem MeSH
β-Cyclodextrin functionalized PEGylated porous silica nanoparticles KIT-6 (denoted as [β-CD@PEGylated KIT-6] NPs) is synthesized and evaluated as an efficient and reliable pH-sensitive nano-carrier. Curcumin (CUR), an anticancer drug, has low solubility and stability and these properties diminished its bioavailability. One way to overcome this problem is employing nano-carrier for delivery of CUR. In this study, the novel [β-CD@PEGylated KIT-6] NPs nano-carrier was employed for CUR delivery successfully. The nano-DDS was characterized using different techniques such as X-ray powder diffraction (XRD), transmission and scanning electron microscopy (TEM and SEM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimeter (DSC), N2 adsorption–desorption measurement, and dynamic light scattering (DLS). In this study, first, the combination of central composite design (CCD) and response surface methodology (RSM) was used to achieve the optimal condition of the loading step with investigation of two important factors: the loading time and the weight ratio of drug to nano-carrier. Maximum loading efficiency 88.55% was obtained at 43 h of loading time and 1.22 of the weight ratio. Then CUR was loaded onto the nano-carrier at this optimal condition and its released was investigated by CCD-RSM. The maximum drug release was obtained at 5.16 of pH and 107 h of release time.
- MeSH
- beta-cyklodextriny * MeSH
- kurkumin * MeSH
- lékové transportní systémy MeSH
- léky s prodlouženým účinkem * chemická syntéza chemie MeSH
- nádorové buněčné linie účinky léků MeSH
- nanočástice MeSH
- nosiče léků chemie MeSH
- oxid křemičitý MeSH
- poréznost MeSH
- protinádorové látky chemická syntéza chemie MeSH
- uvolňování léčiv MeSH
- Publikační typ
- práce podpořená grantem MeSH
pH-dependent sustained-release Tulsion® microspheres bearing clarithromycin were prepared using quasi-emulsion solvent diffusion method with thermocoat L 30 D 55 as a release retardant. Both, clarithromycin and thermocoat L 30 D 55, were found to be non-hemolytic during in vitro toxicity assay against human red blood cells. Ratiometric optimization of different solvents using phase diagrams was performed on amount of good solvent, bridging liquid, dispersing liquid and poor solvent. The developed microspheres were evaluated for the recovery (67.27 ± 3.3%), average particle size (52.0 ± 0.46 μm) and encapsulation efficiency (61.0 ± 3.1%). Scanning electron microscopy and transmission electron microscopy revealed that the microspheres were smooth in surface and spherical in shape, respectively. The drug release study was conducted at different pH of GIT and it gave a pH dependent release for clarithromycin. The bioavailability study revealed increased AUC (2 fold) and half-life (1.2 fold) of microspheres as compared to plain drug. The manuscript reported the debut work on thermocoat L 30 D 55 based novel drug delivery system, the polymer is safe to be used, quasi emulsion spherical crystallization technique is a good technique to prepare microspheres, the prepared microspheres provides sustain release profile as well as targeting to colon.
- MeSH
- biologická dostupnost MeSH
- erytrocyty účinky léků MeSH
- farmaceutická chemie metody MeSH
- gastrointestinální trakt radiografie MeSH
- klarithromycin farmakokinetika MeSH
- koncentrace vodíkových iontů MeSH
- krysa rodu rattus MeSH
- krystalizace metody MeSH
- kyseliny polymethakrylové * toxicita MeSH
- léky s prodlouženým účinkem * farmakokinetika chemická syntéza chemie MeSH
- mikrosféry MeSH
- rozpouštědla chemie MeSH
- rozpustnost MeSH
- stabilita léku MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Injectable depot formulations are aimed at providing long-term sustained release of a drug into systemic circulation, thus reducing plasma level fluctuations and improving patient compliance. The particle size distribution of the formulation in the form of suspension is a key parameter that controls the release rate. In this work, the process of wet stirred media milling (ball milling) of a poorly water-soluble substance has been investigated with two main aims: (i) to determine the parametric sensitivity of milling kinetics; and (ii) to develop scale-up methodology for process transfer from batch to flow-through arrangement. Ball milling experiments were performed in two types of ball mills, a batch mill with a 30ml maximum working volume, and a flow-through mill with a 250ml maximum working volume. Milling parameters were investigated in detail by methodologies of QbD to map the parametric space. Specifically, the effects of ball size, ball fill level, and rpm on the particle breakage kinetics were systematically investigated at both mills, with an additional parameter (flow-rate) in the case of the flow-through mill. The breakage rate was found to follow power-law kinetics with respect to dimensionless time, with an asymptotic d50 particle size in the range of 200-300nm. In the case of the flow-through mill, the number of theoretical passes through the mill was found to be an important scale-up parameter.
High-molecular-weight star polymer drug nanocarriers intended for the treatment and/or visualisation of solid tumours were synthesised, and their physico-chemical and preliminary in vitro biological properties were determined. The water-soluble star polymer carriers were prepared by the grafting of poly(amido amine) (PAMAM) dendrimers by hetero-telechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, synthesised by the controlled radical Reversible Addition Fragmentation chain Transfer (RAFT) polymerisation. The well-defined star copolymers with Mw values ranging from 2 · 10(5) to 6 · 10(5) showing a low dispersity (approximately 1.2) were prepared in a high yield. A model anticancer drug, doxorubicin, was bound to the star polymer through a hydrazone bond, enabling the pH-controlled drug release in the target tumour tissue. The activated polymer arm ends of the star copolymer carrier enable a one-point attachment for the targeting ligands and/or a labelling moiety. In this study, the model TAMRA fluorescent dye was used to prove the feasibility of the polymer carrier visualisation by optical imaging in vitro. The tailor-made structure of the star polymer carriers should facilitate the synthesis of targeted polymer-drug conjugates, even polymer theranostics, for simultaneous tumour drug delivery and imaging.
- MeSH
- dendrimery * chemická syntéza chemie farmakokinetika farmakologie MeSH
- doxorubicin * chemie farmakokinetika farmakologie MeSH
- léky s prodlouženým účinkem chemická syntéza chemie farmakokinetika farmakologie MeSH
- lidé MeSH
- methakryláty * chemie farmakokinetika farmakologie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory * farmakoterapie metabolismus patologie MeSH
- nanočástice chemie ultrastruktura MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hypoglykemické epizody jsou závažné a časté komplikace u obou typů diabetu mellitu. Riziko hypoglykemických stavů lze ovlivnit lékovou formu v podobě potahovaných pelet, které uvolní glukosu se zpožděním tak, aby bylo dosaženo odhadovaného maximálního účinku antidiabetika. Pelety, dále určené pro potažení membránou z ethylcelulosy, obsahovaly jednotlivě čtyři osmoticky aktivní látky: kroskarmelosu sodnou sůl (Ac-Di-Sol?), směs mikrokrystalické celulosy a karmelosy sodné soli (Avicel? RC 591), makrogol 6000 a karboxymethylškrob sodnou sůl (Vivastar? P 5000). Cílem bylo zvýšit obsah glukosy v peletách, a minimalizovat tak jejich objem pro snadnou aplikaci. Obsah glukosy v peletových jádrech se podařilo zvýšit ze 45 až na 75. resp. 80 % u všech složení. Všechny vzorky měly vyhovující mechanické i tokové vlastnosti nezbytné pro proces jejich obalování. Nejvyšších hodnot sféricity bylo dosaženo u vzorku pelet s obsahem 80 % glukosy, 15 % Avicelu? PH 101 a 5 % karboxymethylškrobu sodné soli s nižším středním průměrem částic a u vzorku pelet s obsahem 75 % glukosy a 25 % Avicelu? RC 591 s vyšším středním průměrem částic. Klíčová slova: hyperglykémie - prodloužené uvolňování - glukosa
Hypoglycemic episodes are a frequent and serious complication in both types of diabetes mellitus. The risk of hypoglycemic conditions can be managed by a coated pellet dosage form, which can release glucose in a delayed regime to achieve the maximum estimated effect of antidiabetics. The pellet cores, intended for coating with ethylcellulose, were prepared consisting of four osmotically active excipients: crosscarmellose (Ac-Di-Sol?), a mixture of microcrystalline cellulose and carmellose sodium (Avicel? RC 591), carboxymethyl starch sodium (Vivastar? P 5000) and macrogol 6000, respectively. The aim of this study was to increase the glucose content in the pellets to minimize their volume and to improve the administration to the patients. The content of glucose in the pellet cores was increased from 45 to 75 or 80%, respectively, for all compositions. All pellet samples had satisfactory mechanical and flow properties required for the coating process. The highest values of sphericity were achieved in the lower mean particle size sample containing 80% of glucose, 15% of Avicel? PH 101 and 5% of carboxymethyl starch sodium and the higher mean particle size sample containing 75% of glucose and 25% of Avicel? RC 591. Key words: hypoglycemia - delayed release - glucose
- MeSH
- celulosa MeSH
- diabetes mellitus MeSH
- enterosolventní tablety chemická syntéza MeSH
- glukosa * MeSH
- hypoglykemie * prevence a kontrola MeSH
- hypoglykemika chemická syntéza MeSH
- léky s prodlouženým účinkem * chemická syntéza MeSH
- lidé MeSH
- nosiče léků * MeSH
- polyethylenglykoly MeSH
- pomocné látky MeSH
- povrchově aktivní látky MeSH
- povrchové vlastnosti MeSH
- příprava léků * metody MeSH
- rozpouštědla MeSH
- rozpustnost MeSH
- sodná sůl karboxymethylcelulosy MeSH
- velikost částic MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
