Controlled release floating multiparticulates of metoprolol succinate by hot melt extrusion

YesWe present hot melt extrusion (HME) for the design of floating multiparticulates. Metoprolol succinate was selected as the model drug. Our foremost objective was to optimize the components Eudragit® RS PO, polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) to balance both buoyancy and controlled release. Gas generated by sodium bicarbonate in acidic medium was trapped in the polymer matrix to enable floating. Eudragit® RS PO and PEO with sodium bicarbonate resulted in multiparticulates which exhibited rapid flotation within 3 minutes but inadequate total floating time (TFT) of 3 hours. Addition of HPMC to the matrix did not affect floating lag time (FLT), moreover TFT increased to more than 12 hours with controlled release of metoprolol succinate. Floating multiparticulates exhibited t50% of 5.24 hours and t90% of 10.12 hours. XRD and DSC analysis revealed crystalline state of drug while FTIR suggested nonexistence of chemical interaction between the drug and the other excipients. The assay, FLT, TFT and the drug release of the multiparticulates were unchanged when stored at 40 °C/75%RH for 3 months confirming stability. We present floating multiparticulates by HME which could be extrapolated to a range of other drugs. Our approach hence presents platform technology for floating multiparticulates

Polymorphs of Curcumin and Its Cocrystals With Cinnamic Acid

YesWe report formation of polymorphs and new eutectics and cocrystals of curcumin, a sparingly water-soluble active component in turmeric, structurally similar to cinnamic acid. The curcumin polymorphs were formed using liquid antisolvent precipitation, where acetone acted as a solvent and water was used as the antisolvent. The metastable form 2 of curcumin was successfully prepared in varied morphology over a wide range of solvent-to-antisolvent ratio and under acidic pH conditions. We also report formation of new eutectics and cocrystals of curcumin with cinnamic acid acting as a coformer. The binary phase diagrams were studied using differential scanning calorimetry and predicted formation of the eutectics at the curcumin mole fraction of 0.15 and 0.33, whereas a cocrystal was formed at 0.3 mole fraction of curcumin in the curcumin–cinnamic acid mixture. The formation of the cocrystal was supported with X-ray powder diffraction, the enthalpy of fusion values, Fourier-transform infrared spectroscopy, and scanning electron microscopy. The hydrogen bond interaction between curcumin and cinnamic acid was predicted from Fourier-transform infrared spectra, individually optimized curcumin and cinnamic acid structures by quantum mechanical calculations using Gaussian-09 and their respective unit cell packing structures

Priprava i evaluacija plutajućih matriksa rizedronat natrija Gelucire® 39/01

Incorporation of bisphosphonates in the lipid reduces gastric irritation. Only gastric retention with sustained release allows the drug to reach the duodenum and jejunum and improves the availability of bisphosphonates. Risedronate sodium and Gelucire® 39/01 floating matrices were prepared using melt solidification. The sustained release floating matrices were evaluated for in vitro and in vivo floating ability and in vitro drug release. Ageing of the matrices was studied by differential scanning calorimetry, hot stage polarizing microscopy, scanning electron microscopy and in vitro drug release. Ageing causes changes in the crystal structure of the Gelucire®, which is responsible for increase in drug release.Uklapanje bisfosfonata u lipide smanjuje iritaciju želuca. Samo zadržavanje u želucu s usporenim oslobađanjem omogućava da ljekovita tvar dospije u duodenum i jejunum i povećava bioraspoloživost bisfosfonata. Rizedronat natrij i Gelucire® 39/01 plutajući matriksi pripravljeni su metodom taljenja i očvršćivanja. Proučavana je sposobnost plutanja pripremljenih matriksa in vitro i in vivo te oslobađanje ljekovite tvari. Starenje matriksa proučavano je diferencijalnom pretražnom kalorimetrijom, polarizirajućom mikroskopijom s vrućom pločom i pretražnom elektronskom mikroskopijom. Starenje uzrokuje promjene u kristalnoj strukturi Gelucire® zbog kojih se povećava oslobađanje ljekovite tvari

Priprava i evaluacija plutajućih matriksa rizedronat natrija Gelucire® 39/01

Incorporation of bisphosphonates in the lipid reduces gastric irritation. Only gastric retention with sustained release allows the drug to reach the duodenum and jejunum and improves the availability of bisphosphonates. Risedronate sodium and Gelucire® 39/01 floating matrices were prepared using melt solidification. The sustained release floating matrices were evaluated for in vitro and in vivo floating ability and in vitro drug release. Ageing of the matrices was studied by differential scanning calorimetry, hot stage polarizing microscopy, scanning electron microscopy and in vitro drug release. Ageing causes changes in the crystal structure of the Gelucire®, which is responsible for increase in drug release.Uklapanje bisfosfonata u lipide smanjuje iritaciju želuca. Samo zadržavanje u želucu s usporenim oslobađanjem omogućava da ljekovita tvar dospije u duodenum i jejunum i povećava bioraspoloživost bisfosfonata. Rizedronat natrij i Gelucire® 39/01 plutajući matriksi pripravljeni su metodom taljenja i očvršćivanja. Proučavana je sposobnost plutanja pripremljenih matriksa in vitro i in vivo te oslobađanje ljekovite tvari. Starenje matriksa proučavano je diferencijalnom pretražnom kalorimetrijom, polarizirajućom mikroskopijom s vrućom pločom i pretražnom elektronskom mikroskopijom. Starenje uzrokuje promjene u kristalnoj strukturi Gelucire® zbog kojih se povećava oslobađanje ljekovite tvari

Comparative antioxidant potential of Withania somnifera based herbal formulation prepared by traditional and non-traditional fermentation processes

AbstractBackgroundAshwagandharishtha is a liquid polyherbal formulation traditionally prepared by fermentation process using the flowers of Woodfordia fruticosa. It contains roots of Withania somnifera as a major crude drug. Alcohol generated during the fermentation causes the extraction of water insoluble phytoconstituents. Yeasts present on the flowers are responsible for this fermentation.MethodsTotal nine formulations of ashwagandharishtha were prepared by fermentation process using traditional Woodfordia fruticosa flowers (ASG-WFS) and using yeasts isolated from the same flowers. During fermentation, kinetic of alcohol generation, sugar consumption, changes in pH and withanolides extraction were studied. All the formulations were tested for in vitro antioxidant potential by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging, hydrogen peroxide scavenging and total reducing power assay. The results were compared with standard ascorbic acid.ResultsTraditional formulation (ASG-WFS) showed the highest activity (p < 0.001) relative to other formulations and standard ascorbic acid. ASG-WFS showed significant (DPPH) free radical scavenging (78.75%) and hydrogen peroxide scavenging (69.62%) at the concentration of 1000μg/mL and 100μg/mL, respectively.ConclusionTraditional process is the best process for preparing ashwagandharishtha to obtain significant antioxidant activity

Samoemulzirajući pripravci za peroralnu primjenu simvastatina: Ispitivanja in vitro i in vivo

The objective of the present work was to formulate a self-emulsifying drug delivery system (SEDDS) for simvastatin, which is widely used in the treatment of hypercholesterolemia and dyslipidemia as an adjunct to diet. Simvastatin SEDDS were formulated using a 1:1 (V/V) mixture of diesters of caprylic/capric acids and polyglycolyzed glycerides with varying concentrations of polyoxy 35 castor oil and C8/C10 mono-/diglycerides. The developed SEDDS were evaluated for turbidimetry, droplet size analysis, drug content and in vitro diffusion profiles. In vivo performance of the optimized formulation was evaluated in rats using pharmacodynamic marker parameters like plasma total cholesterol (CH), triglycerides (TG) and high-density lipoprotein (HDL-CH) for 21 days. SEDDS containing 9.1% (m/m) simvastatin and 23%, (m/m) of each excipient showed minimum mean droplet size (124 nm) and optimal drug diffusion. This test formulation showed significant reduction in plasma CH and TG (around 5-fold and 4-fold, respectively), while HDL-CH concentration was markedly higher (2-fold) compared a reference simvastatin suspension formulation after oral administration for 21 days of study. Test formulation has shown enhanced pharmacodynamic performance compared to reference formulation in rats. The study illustrated the potential of simvastatin SEDDS for oral administration and its biopharmaceutic performance.Cilj rada bio je pripraviti samoemulzirajući sustav za isporuku lijeka (SEDDS) za simvastatin, hipolipemik koji se uz dijetu upotrebljava u terapiji hiperkolesterolemije i dislipidemije. Simvastatin SEDDS su pripravljene koristeći smjesu 1:1 (V/V) diestera kaprilne i kaprinske kiseline i poliglikoliziranih glicerida s različitim koncentracijama polioksil 35 kastorovog ulja i C8/C10 mono-/diglicerida. Pripravcima su ispitana turbidimetrijska svojstva, veličina čestica, udio lijeka i in vitro difuzijski profil. U pokusima in vivo na štakorima praćeni su parametri farmakodinamičkih markera kao što su ukupni kolesterol u plazmi (CH), trigliceridi (TG) i lipoproteini velike gustoće (HDL-CH) tijekom 21 dana. Pripravci koji sadrže 9,1% (m/m) simvastatina i 23% (m/m) svake od pomoćnih tvari imaju najmanju prosječnu veličinu čestica (124 nm) i iz njih je difuzija lijeka optimalna. Ispitivani pripravci značajno snizuju CH i TG u plazmi (5, odnosno 4 puta), dok je koncentracija HDL-CH ostaje izrazito visoka, 2 puta viša u usporedbi s referentnom suspenzijom simvastatina poslije peroralne primjene tijekom 21 dan. Ispitivani pripravci imaju bolji farmakodinamički profil u odnosu na referentni pripravak pa imaju veliki potencijal za peroralnu primjenu simvastatina

Ispitivanje vosku sličnih svojstava ibuprofena kao veziva

The study investigates ibuprofen with wax-like properties as a multifunctional agent (as an active component and as a melt binder). Binding efficiency was compared with granules prepared by wet granulation using polyvinylpyrollidone (PVP K-30) as a binder for micromeritic, physical and mechanical properties such as angle of repose, particle size distribution Carr’s index, Hausner’s ratio, crushing strength, percentage fines, Heckel plot study and tensile strength. To check the binder distribution during melt granulation, content uniformity was determined. To check changes in the physical state of ibuprofen, XRPD, DSC and FTIR studies were carried out. The present study underlines the fact that ibuprofen may be adopted as a binder in ibuprofen formulations using the melt granulation techniqueSvrha rada je ispitivanje vosku sličnih svojstava ibuprofena, tvari s višeznačnom funkcijom (ljekovita tvar i vezivo pri granulaciji). Vezivna svojstva uspoređivana su s granulama pripravljenim vlažnom granulacijom s polivinilpirolidonom (PVP K-30) kao vezivom, ispitivanjem mikrometričkih, fizikalnih i mehaničkih svojstava kao što su sipkost materijala, Carrov indeks distribucije veličine čestica, Hausnerov parameter, otpornost na vlak. Da bi se ispitala distribucija veziva tijekom granulacije taljenjem određivana je ujednačenost sadržaja. Za praćenje promjena fizikalnih svojstava ibuprofena snimljeni su XRPD, DSC, FTIR spektri. Istraživanja ukazuju da se ibuprofen može koristiti kao vezivo u ljekovitim pripravcima ibuprofena u kojima se primjenjuje granulacija taljenjem

Ispitivanje vosku sličnih svojstava ibuprofena kao veziva

The study investigates ibuprofen with wax-like properties as a multifunctional agent (as an active component and as a melt binder). Binding efficiency was compared with granules prepared by wet granulation using polyvinylpyrollidone (PVP K-30) as a binder for micromeritic, physical and mechanical properties such as angle of repose, particle size distribution Carr’s index, Hausner’s ratio, crushing strength, percentage fines, Heckel plot study and tensile strength. To check the binder distribution during melt granulation, content uniformity was determined. To check changes in the physical state of ibuprofen, XRPD, DSC and FTIR studies were carried out. The present study underlines the fact that ibuprofen may be adopted as a binder in ibuprofen formulations using the melt granulation techniqueSvrha rada je ispitivanje vosku sličnih svojstava ibuprofena, tvari s višeznačnom funkcijom (ljekovita tvar i vezivo pri granulaciji). Vezivna svojstva uspoređivana su s granulama pripravljenim vlažnom granulacijom s polivinilpirolidonom (PVP K-30) kao vezivom, ispitivanjem mikrometričkih, fizikalnih i mehaničkih svojstava kao što su sipkost materijala, Carrov indeks distribucije veličine čestica, Hausnerov parameter, otpornost na vlak. Da bi se ispitala distribucija veziva tijekom granulacije taljenjem određivana je ujednačenost sadržaja. Za praćenje promjena fizikalnih svojstava ibuprofena snimljeni su XRPD, DSC, FTIR spektri. Istraživanja ukazuju da se ibuprofen može koristiti kao vezivo u ljekovitim pripravcima ibuprofena u kojima se primjenjuje granulacija taljenjem

Coformer Replacement as an Indicator for Thermodynamic Instability of Cocrystals: Competitive Transformation of Caffeine:Dicarboxylic Acid

yesThe thermodynamic stability of caffeine (CA) cocrystals with dicarboxylic acids (DAs) as coformers was investigated in the presence of a range of structurally related dicarboxylic acids (SRDs). Two experimental conditions (slurry and dry-grinding) were studied for mixing the cocrystal and the SRD additive. The additives oxalic, malonic and glutaric acid led to the replacement of the acid coformer for certain cocrystals. Interestingly, a change in stoichiometry was observed for the CA:maleic acid system. A stability order among the cocrystals was established depending on their tendency to replace the coformer. To understand the factors controlling the relative stabilities, lattice energies were calculated using dispersion corrected Density Functional Theory (DFT). Gibbs free energy changes were calculated from experimental solubilities. The observed stability order corroborated well with lattice energy and Gibbs free energy computations

Improving Stability of Effervescent Products by Co-Crystal Formation: A Novel Application of Crystal Engineered Citric Acid

YesThe major concern of the physical and chemical instability of effervescent products during manufacturing and storage is addressed through a co-crystallization strategy. Citric acid (CA) and sodium bicarbonate (SBC) are the essential components of effervescent products. CA is hygroscopic and led to an uncontrollable autocatalytic chain reaction with SBC in the presence of a small amount of moisture, causing product instability. The acid···amide dimer bond and layered structure of the citric acid-nicotinamide co-crystal restricts interaction of moisture with CA, making it nonhygroscopic, and improves the stability of effervescent products. The comparative study of effervescent products containing CA in its free form and as a co-crystal suggests a significant advantage of the use of co-crystal in effervescent products. This finding is supported by the mechanistic understanding developed through GAB and Y&N models obtained from moisture sorption data along with the computational investigations into moisture interactions with different crystal surfaces