Spray Drying as an Approach for Enhancement of Dissolution and Bioavailability of Raloxifene Hydrochloride.

The present study investigated the effect of spray drying raloxifene HCl (RHCL) with different classes of hydrophilic carriers (different grades of polyvinyl pyrrolidones) and cellulosic polymers) in order to determine the potential effect on dissolution rate and bioavailability of RHCL. Pre-formulation studies were conducted to select the appropriate carriers and drug:carrier ratio for preparing the spray dried compositions.The solid state interactions of the spray dried mixtures were evaluated by DSC & XRD. Preformulation studies revealed that amorphous compositions of RHCL could be obtained only with Plasdones (K12, K29/32 and S630). DSC studies showed that the crystalline nature of RHCL was significantly reduced on spray drying. Significant enhancement in dissolution rate was observed with the prepared spray dried compositions and out of the three grades of Plasdone, Plasdone K12 demonstrated the maximum enhancement in rate of release of RHCL. The pharmacokinetics of spray dried composition (1:1 RHCL: K12) and pure RHCL was evaluated following oral administration (25 mg/kg) in healthy female Sprague Dawley rats. The extent of the mean plasma exposures of RHCL was 7-fold higher in animals treated with spray dried mixture of RHCL, K12 (1:1) compared to animals treated with RHCL. Spray drying of RHCL with Plasdones, especially Plasdone K12, reduced drug crystallinity, increased the rate and extent of dissolution, and improved bioavailability

Atypical presentation of angiosarcoma of the scalp in the setting of Human Immunodeficiency Virus (HIV)

<p>Abstract</p> <p>Background</p> <p>Angiosarcoma of the head and neck is an uncommon, aggressive malignant entity most commonly found in elderly Caucasian males. We present a case in a young black female with co-existing HIV. The atypical gender, age and race of the patient reflect the unusual clinical presentation of this case of angiosarcoma, attributable to the patient's HIV status.</p> <p>Case presentation</p> <p>A 22 year old patient presented with a large unresectable lesion over the occiput with surrounding ulceration, satellite lesions and associated lymphadenopathy. She is HIV-infected with a CD4 count of 360 cells/μl. She was not on antiretroviral treatment based on South African treatment guidelines advocating antiretroviral treatment when the CD4 count is below 200 cells/μl, in the absence of other AIDS-defining illnesses.</p> <p>The patient was treated with a course of ifosfamide and anthracyline based chemotherapy. Disease progression was noted on chemotherapy and she was subsequently palliated with a course of radiotherapy. She had a satisfactory response with an improvement in local symptoms. She is currently receiving symptomatic care.</p> <p>Conclusions</p> <p>South Africa is at the epicenter of the HIV epidemic. Consequently, the management of patients in the field of oncology in our clinical practice is often burdened with malignancies manifesting with an atypical disease presentation and clinical course.</p

Comprimidos de liberación inmediata de Valsartán y Efavirenz: El papel de la concentración de superdisgregantes

The objective of this study was to formulate directly compressible fast disintegrating tablets of poorly water solubledrugs with different extent of drug solubilities, like valsartan and efavirenz, as model drugs. Effect of varying concentrationsof different superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate ondisintegration time and in vitro drug dissolution was studied. The disintegration time of the best immediate release tabletformulation among those tested was observed to be 21.5±1.26 sec and 20.16±0.85 sec for valsartan and efavirenz tabletscontaining 20% of Crospovidone, respectively. Drug release (from both valsartan and Efavirenz tablets) was faster fromformulations containing crospovidone compared to the other formulation. The effect was more apparent in Efavirenz,which has lesser aqueous solubility than valsartan. It was observed that 20% crospovidone was required to achieve80% drug release from efavirenz tablets. Differential scanning calorimetric studies did not indicate any drug-excipientincompatibility. In conclusion, directly compressible fast disintegrating tablets of valsartan and efavirenz with shorterdisintegration times and high dissolution rate were obtained and crospovidone seemed to be a better disintegrant forboth valsartan and efavirenz, based on disintegration time and T80% values obtained.El objetivo de este estudio fue formular comprimidos de rápida disgregación, obtenidos mediante compresión directa,de fármacos con baja solubilidad en agua y diferentes grados de solubilidad, tomando como modelo Valsartány Efavirenz. Se estudió el efecto de diversas concentraciones de diferentes superdisgregantes como crospovidona,croscarmelosa sódica y glicolato sódico de almidón sobre el tiempo de disgregación y la disolución del fármaco invitro. Se observó que el tiempo de disgregación del comprimido con mejor liberación inmediata, de entre todaslas formulaciones probadas, fue de 21,5 ± 1,26 s y 20,16 ± 0,85 s para los comprimidos de Valsartán y Efavirenz,respectivamente que contenían, en ambos casos, un 20% de crospovidona. La liberación del fármaco (tanto en loscomprimidos de Valsartán como Efavirenz) fue más rápida en el caso de las formulaciones con crospovidona encomparación con la otra formulación. El efecto fue más evidente en el caso de Efavirenz, cuya solubilidad en aguaes menor que la de Valsartán. Se observó que era necesario un 20% de crospovidona para obtener una liberacióndel fármaco del 80% en comprimidos de Efavirenz. Los estudios por calorimetría diferencial de barrido no indicaronninguna incompatibilidad fármaco-excipiente. En conclusión, se obtuvieron por compresión directa comprimidosde rápida disgregación de Valsartán y Efavirenz con tiempos de disgregación más cortos y una alta velocidad dedisolución. Además, la crospovidona resultó ser un mejor disgregante tanto para Valsartán como para Efavirenz,de acuerdo con el tiempo de disgregación y los valores T80% obtenidos

Immediate Release Tablets of Valsartan and Efavirenz: role of Concentration of Superdisintegrants

El objetivo de este estudio fue formular comprimidos de rápida disgregación, obtenidos mediante compresión directa, de fármacos con baja solubilidad en agua y diferentes grados de solubilidad, tomando como modelo Valsartán y Efavirenz. Se estudió el efecto de diversas concentraciones de diferentes superdisgregantes como crospovidona, croscarmelosa sódica y glicolato sódico de almidón sobre el tiempo de disgregación y la disolución del fármaco in vitro. Se observó que el tiempo de disgregación del comprimido con mejor liberación inmediata, de entre todas las formulaciones probadas, fue de 21,5 ± 1,26 s y 20,16 ± 0,85 s para los comprimidos de Valsartán y Efavirenz, respectivamente que contenían, en ambos casos, un 20% de crospovidona. La liberación del fármaco (tanto en los comprimidos de Valsartán como Efavirenz) fue más rápida en el caso de las formulaciones con crospovidona en comparación con la otra formulación. El efecto fue más evidente en el caso de Efavirenz, cuya solubilidad en agua es menor que la de Valsartán. Se observó que era necesario un 20% de crospovidona para obtener una liberación del fármaco del 80% en comprimidos de Efavirenz. Los estudios por calorimetría diferencial de barrido no indicaron ninguna incompatibilidad fármaco-excipiente. En conclusión, se obtuvieron por compresión directa comprimidos de rápida disgregación de Valsartán y Efavirenz con tiempos de disgregación más cortos y una alta velocidad de disolución. Además, la crospovidona resultó ser un mejor disgregante tanto para Valsartán como para Efavirenz, de acuerdo con el tiempo de disgregación y los valores T80% obtenidos.The objective of this study was to formulate directly compressible fast disintegrating tablets of poorly water soluble drugs with different extent of drug solubilities, like valsartan and efavirenz, as model drugs. Effect of varying concentrations of different superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate on disintegration time and in vitro drug dissolution was studied. The disintegration time of the best immediate release tablet formulation among those tested was observed to be 21.5±1.26 sec and 20.16±0.85 sec for valsartan and efavirenz tablets containing 20% of Crospovidone, respectively. Drug release (from both valsartan and Efavirenz tablets) was faster from formulations containing crospovidone compared to the other formulation. The effect was more apparent in Efavirenz, which has lesser aqueous solubility than valsartan. It was observed that 20% crospovidone was required to achieve 80% drug release from efavirenz tablets. Differential scanning calorimetric studies did not indicate any drug-excipient incompatibility. In conclusion, directly compressible fast disintegrating tablets of valsartan and efavirenz with shorter disintegration times and high dissolution rate were obtained and crospovidone seemed to be a better disintegrant for both valsartan and efavirenz, based on disintegration time and T80% values obtained

Priprava i in vitro karakterizacija plutajućih zrnaca acetohidroksamske kiseline za iskorjenjivanje H. pylori

Gellan based floating beads of acetohydroxamic acid (AHA) were prepared by the ionotropic gellation method to achieve controlled and sustained drug release for treatment of Helicobacter pylori infection. The prepared beads were evaluated for diameter, surface morphology and encapsulation efficiency. Formulation parameters like concentrations of gellan, chitosan, calcium carbonate and the drug influenced the in vitro drug release characteristics of beads. Drug and polymer interaction studies were carried out using differential scanning calorimetry. Chitosan coating increased encapsulation efficiency of the beads and reduced the initial burst release of the drug from the beads. Kinetic treatment of the drug release data revealed a matrix diffusion mechanism. Prepared floating beads showed good antimicrobial activity (in vitro H. pylori culture) as potent urease inhibitors. In conclusion, an oral dosage form of floating gellan beads containing AHA may form a useful stomach site specific drug delivery system for the treatment of H. pylori infection.Metodom ionotropskog želiranja pripravljena su plutajuća zrnca acetohidroksamske kiseline (AHA) na bazi gelana za kontrolirano i usporeno oslobađanje ljekovite tvari, namijenjena za liječenje infekcija uzrokovanih Helicobacter pylori. Pripravljenim zrncima proučavani su dijametar, površinska morfologija i sposobnost inkapsuliranja. Koncentracija gelana, kitozana, kalcijeva karbonata i ljekovite tvari utjecala je na oslobađanje in vitro. Interakcija između ljekovite tvari i polimera praćena je diferencijalnom pretražnom kalorimetrijom. Oblaganje zrnaca kitozanom povećalo je učinkovitost inkapsuliranja i smanjilo početno naglo oslobađanje. Oslobađanje ljekovite tvari slijedilo je mehanizam difuzije matriksa. Plutajuća zrnca s AHA pokazala su antimikrobno djelovanje in vitro na kulturi H. pylori kao snažni inhibitori ureaze. Može se zaključiti da su plutajuća zrnca s AHA na bazi gelana pogodna za specifičnu isporuku u želucu te korisna u terapiji infekcija uzrokovanih H. pylori

NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants

Salicylic acid (SA) is a plant immune signal produced upon pathogen challenge to induce systemic acquired resistance (SAR). It is the only major plant hormone for which the receptor has not been firmly identified. SAR in Arabidopsis requires the transcription cofactor NPR1 (nonexpresser of PR genes 1), whose degradation serves as a molecular switch for SAR. Here we show that NPR1 paralogues, NPR3 and NPR4, are SA receptors that bind SA with different affinities and function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the npr3 npr4 mutant accumulates higher levels of NPR1 and is insensitive to SAR induction. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge

The additional value of TGFβ1 and IL-7 to predict the course of prostate cancer progression

Background: Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of the prostate cancer diagnosed. Since cytokines have been associated with the biology of cancer and its prognosis, we determined whether transforming growth factor beta 1 (TGFβ1), interleukin-7 (IL-7) receptor and IL-7 levels add additional prognostic information with regard to prostate cancer

p53 Target Gene SMAR1 Is Dysregulated in Breast Cancer: Its Role in Cancer Cell Migration and Invasion

Tumor suppressor SMAR1 interacts and stabilizes p53 through phosphorylation at its serine-15 residue. We show that SMAR1 transcription is regulated by p53 through its response element present in the SMAR1 promoter. Upon Doxorubicin induced DNA damage, acetylated p53 is recruited on SMAR1 promoter that allows activation of its transcription. Once SMAR1 is induced, cell cycle arrest is observed that is correlated to increased phospho-ser-15-p53 and decreased p53 acetylation. Further we demonstrate that SMAR1 expression is drastically reduced during advancement of human breast cancer. This was correlated with defective p53 expression in breast cancer where acetylated p53 is sequestered into the heterochromatin region and become inaccessible to activate SMAR1 promoter. In a recent report we have shown that SMAR1 represses Cyclin D1 transcription through recruitment of HDAC1 dependent repressor complex at the MAR site of Cyclin D1 promoter. Here we show that downmodulation of SMAR1 in high grade breast carcinoma is correlated with upregulated Cyclin D1 expression. We also established that SMAR1 inhibits tumor cell migration and metastases through inhibition of TGFβ signaling and its downstream target genes including cutl1 and various focal adhesion molecules. Thus, we report that SMAR1 plays a central role in coordinating p53 and TGFβ pathways in human breast cancer

Priprava i in vitro karakterizacija mikrosfera amoksicilina dobivenih metodom sušenja sprejom

The purpose of the present study was to design mucoadhesive chitosan microspheres containing amoxycillin. Chitosan microspheres with a small particle size and good sphericity were prepared by a spray-drying method followed by chemical treatment with a chemical crosslinking agent (glutaraldehyde). Parameters affecting the extent of crosslinking were the crosslinking time and the concentration of the crosslinker agent. Crosslinked spray-dried chitosan microspheres were analyzed for their morphological aspects, particle size, drug entrapment efficiency, swelling percent and in vitro drug release. Batch M4 with a drug polymer ratio of 1:2, dissolved in minimum concentration of acetic acid solution treated with glutraldehyde, was found to be optimal giving controlled drug release for 10 h. It was found that both the increase of glutaraldehyde concentration and crosslinking duration decreased the swelling capacity of chitosan microspheres. This could be directly correlated to drug release from the microspheres.Cilj ovog rada bio je priprava mukoadhezivnih kitozanskih mikrosfera amoksicilina. Mikrosfere male veličine čestica i dobre sferičnosti pripravljene su metodom sušenja sprejom, te obradom s glutaraldehidom kao sredstvom za umrežavanje. Stupanj umrežavanja ovisio je o vremenu umrežavanja i koncentraciji sredstva za umrežavanje. Umreženim kitozanskim mikrosferama određen je oblik, veličina čestica, količina uklopljenog lijeka, postotak bubrenja i in vitro oslobađanje ljekovite tvari. Pripravak M4 s optimalnim svojstvima i kontroliranim oslobađanjem amoksicilina tijekom 10 sati pripravljen je pomoću smjese polimera omjera 1:2 otopljenih u razrijeđenoj octenoj kiselini, te umreženih pomoću glutraldehida. Povećanje koncentracije glutaraldehida i trajanja umrežavanja smanjuje sposobnost bubrenja kitozanskih mikrosfera, što je u izravnoj korelaciji s oslobađanjem lijeka iz mikročestica