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

Utjecaj superdezintegratora na oslobađanje efavirenca iz tableta

Efavirenz (EFV) tablets of different doses were prepared by a wet granulation process using different superdisintegrants such as crosscarmellose sodium (CCS), sodium starch glycollate (SSG) and crosspovidone (CP) to evaluate the role of different disintegrants on the in vitro release of EFV. Further, the mode of addition of disintegrants on EFV dissolution from tablets containing 600 mg of the drug was evaluated by incorporating the disintegrant extragranularly (EG), intragranularly (IG) or distributing them equally (IG and EG). In vitro dissolution of the prepared tablets was conducted using the recommended medium and a dissolution medium developed in-house, which had the propensity to discriminate between the formulations. The t50 and t80 values were indicative of the fact that drug release was faster from tablet formulations containing CP. CP was able to release the drug faster than the other two disintegrants in both dissolution media and the drug release was unaffected by the mode of CP addition.U radu je opisana priprava tableta s različitim dozama efavirenca (EFV) metodom vlažne granulacije. Za tabletiranje korišteni su različiti superdezintegratori, poput natrijeve kroskarameloze (CCS), natrijeva škrobnog glikolata (SSG) i krospovidona (CP), kako bi se procijenio utjecaj vrste i načina dodavanja dezintegratora na oslobađanje EFV in vitro. U tu svrhu pripravljene su tablete sa 600 mg EFV, a dezintegrator je dodavan ekstragranularno (EG), intragranularno (IG) ili je bio podjednako raspršen (IG i EG). In vitro oslobađanje praćeno je u preporučenom mediju i mediju izrađenom u našem laboratoriju kako bi se uočila razlika između formulacija. Vrijednosti t50 i t80 ukazuju na to da je oslobađanje lijeka brže iz formulacija koje sadrže CP u oba medija. Način dodavanja CP nema utjecaj na oslobađanje lijeka, osim za CCS, gdje se ekstragranularno dodavanje pokazalo povoljnijim

Rural Indian tribal communities: an emerging high-risk group for HIV/AIDS

BACKGROUND: Rural Indian tribes are anthropologically distinct with unique cultures, traditions and practices. Over the years, displacement and rapid acculturation of this population has led to dramatic changes in their socio-cultural and value systems. Due to a poor health infrastructure, high levels of poverty and ignorance, these communities are highly vulnerable to various health problems, especially, communicable diseases including HIV/AIDS. Our study sought to assess knowledge, attitudes and practices regarding sexuality, and the risk factors associated with the spread of HIV/AIDS and STDs among these communities. METHODS: A nested cross sectional study was undertaken as part of the on going Reproductive and Child Health Survey. A total of 5,690 participants age 18–44 were recruited for this study. Data were obtained through home interviews, and focused on socio-demographics, knowledge, attitudes and behaviors regarding sexuality, HIV/AIDS and other STDs. RESULTS: The study revealed that only 22% of adults had even heard of AIDS, and 18 % knew how it is transmitted. In addition, only 5% knew that STDs and AIDS were related to each other. AIDS awareness among women was lower compared to men (14% vs.30 %). Regarding sexual practices, 35% of the respondents reported having had extramarital sexual encounters, with more males than females reporting extramarital affairs. CONCLUSION: Lack of awareness, permissiveness of tribal societies for premarital or extra-marital sexual relationships, and sexual mixing patterns predispose these communities to HIV/AIDS and STD infections. There is a dire need for targeted interventions in order to curtail the increasing threat of HIV and other STDs among these vulnerable populations

Challenges in Diagnosing Intermediate Maple Syrup Urine Disease by Newborn Screening and Functional Validation of Genomic Results Imperative for Reproductive Family Planning

Maple syrup urine disease is caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase, responsible for degradation of leucine, isoleucine, and valine. Biallelic pathogenic variants in BCKDHA, BCKDHB, or DBT genes result in enzyme deficiency. We report the case of a female infant who presented with mild gross motor delay at 4 months, and seizures with hypoglycaemia at 5 months. Newborn screening returned total leucine/isoleucine at the 99.5th centile of the population; however, as second-tier testing reported minimal alloisoleucine, the results were considered inconsistent with MSUD. Plasma amino acid and urine organic acid analyses at 5 months were, however, consistent with a diagnosis of MSUD. A brain MRI showed bilateral symmetrical T2 hyperintense signal abnormalities involving white matter, globus pallidus, thalamus, brainstem, and dentate nuclei with restricted diffusion. A repeat MRI 10 months post-dietary-intervention showed the resolution of these changes and progression in myelination. Her clinical phenotype, including protein tolerance, correlated with intermediate MSUD. Molecular analysis of all three genes identified two variants of uncertain significance, c.434-15_434-4del and c.365A>G (p. Tyr122Cys) in the DBT gene. The rate of leucine decarboxylation in fibroblasts was reduced, but not to the extent observed in classical MSUD patients, supporting an intermediate form of MSUD. Previously reported mRNA splicing studies supported a deleterious effect of the c.434-15_434-4del variant. This functional evidence and confirmation that the variants were in trans, permitted their reclassification as pathogenic and likely pathogenic, respectively, facilitating subsequent prenatal testing. This report highlights the challenges in identifying intermediate MSUD by newborn screening, reinforcing the importance of functional studies to confirm variant pathogenicity in this era of molecular diagnostics