Amjad Khan

Enhancement of dissolution rate of class II drugs (Hydrochlorothiazide); a comparative study of the two novel approaches; solid dispersion and liqui-solid techniques

Liqui-solid technique and solid dispersion formation are two novel approaches for enhancement of dissolution rate of BCS class II drugs. Liqui-solid compact converts a liquid drug or drug solution into a free flowing powder with enhanced dissolution rate. In case of solid dispersion drug is molecularly dispersed in a hydrophilic polymer in solid state. In the present study, Liqui-solid and solid dispersion techniques were applied to enhance the dissolution of the Hydrochlorothiazide. Three formulations of Hydrochlorothiazide were prepared by liqui-solid technique using micro crystalline cellulose as carrier material and colloidal silicon dioxide as coating material. Water, poly ethylene glycol-400 and Tween-60 were used as solvent system. Solid dispersions of Hydrochlorothiazide were prepared by solvent fusion method using PEG-4000 as carrier polymer. Tablets were subjected to evaluation of various physical and chemical characteristics. Dissolution profiles of tablets prepared by the novel techniques were compared with marketed conventional tablets. Model independent techniques including similarity factor, dissimilarity factor and dissolution efficiency were applied for comparison of dissolution profiles. The results obtained indicated that liqui-solid compact formulations were more effective in enhancing the dissolution rate compared with solid dispersion technique. The liqui-solid compacts improved the dissolution rate up to 95% while the solid dispersion increased it to 88%.

Application of SeDeM Expert system in formulation development of effervescent tablets by direct compression

The SeDeM expert system is a pre formulation tool applied for the prediction of the suitability of a material for direct compression. This innovative tool provides an index of good compressibility of the material indicating its aptitude to be compressed by direct compression. In the study the SeDeM expert system has been applied for the prediction of the behavior of the material to be used in the formulation of effervescent tablets by direct compression. Different formulations were developed on the basis of the results of the SeDeM expert system. Various parameters for the material as per the SeDeM expert system were determined according to their official and reported methods. Powder blend for different formulations was evaluated for their rheological properties while tablets were evaluated for various official and unofficial tests. Suitability of the material for direct compression was successfully predicted using the SeDeM expert system. Domperidone was found unsuitable for direct compression. During formulation all excipients responded as they were predicted as per the SeDeM expert system. Tablets produced using the resultant formulations were having sufficient mechanical strength, free of premature effervescence and were capable to be scaled up for commercial manufacturing.

A simple, rapid and sensitive RP-HPLC-UV method for the simultaneous determination of sorafenib & paclitaxel in plasma and pharmaceutical dosage forms: Application to pharmacokinetic study

A simple, economical, fast, and sensitive RP-HPLC-UV method has been developed for the simultaneous quantification of Sorafenib and paclitaxel in biological samples and formulations using piroxicam as an internal standard. The experimental conditions were optimized and method was validated according to the standard guidelines. The separation of both the analytes and internal standard was achieved on Discovery HS C18 column (250mm×4.6mm, 5μm) using Acetonitrile and TFA (0.025%) in the ratio of (65:35V/V) as the mobile phase in isocratic mode at a flow rate of 1ml/min, with a wavelength of 245nm and at a column oven temperature of 25°Cin a short run time of 12min. The limits of detection (LLOD) were 5 and 10ng/ml while the limits of quantification (LLOQ) were 10 and 15ng/ml for sorafenib and paclitaxel, respectively. Sorafenib, paclitaxel and piroxicam (IS) were extracted from biological samples by applying acetonitrile as a precipitating and extraction solvent. The method is linear in the range of 15-20,000ng/ml for paclitaxel and 10-5000ng/ml for sorafenib, respectively. The method is sensitive and reliable by considering both of its intra-day and inter-day co-efficient of variance. The method was successfully applied for the quantification of the above mentioned drugs in plasma. The developed method will be applied towards sorafenib and paclitaxel pharmacokinetics studies in animal models.

From nanoemulsions to self-nanoemulsions, with recent advances in self-nanoemulsifying drug delivery systems (SNEDDS)

ABSTRACT Introduction: Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorly water soluble drugs. Nanotechnology strongly influences the therapeutic performance of hydrophobic drugs and has become an essential approach in drug delivery research. Self-nanoemulsifying drug delivery systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with poor aqueous solubility. Areas covered: The review in its first part shortly describes the LBDDS, nanoemulsions and clarifies the ambiguity between nanoemulsions and microemulsions. In the second part, the review discusses SNEDDS and elaborates on the current developments and modifications in this area without discussing their associated preparation techniques and excipient properties. Expert opinion: SNEDDS have exhibit the potential to increase the bioavailability of poorly water soluble drugs. The stability of SNEDDS is further increased by solidification. Controlled release and supersaturation can be achieved, and are associated with increased patient compliance and improved drug loads, respectively. Presence of biodegradable ingredients and ease of large-scale manufacturing combined with a lot of ‘drug-targeting opportunities’ give SNEDDS a clear distinction and prominence over other solubility enhancement techniques.

Management of Patient Care in Hemodialysis While Focusing on Cardiovascular Disease Events and the Atypical Role of Hyper- and/or Hypotension: A Systematic Review

Background. Hemodialysis related hemodynamic instability is a major but an underestimated issue. Moreover, cardiovascular events are the leading cause of morbidity and mortality associated with blood pressure in hemodialysis patients. However, there have been many controversies regarding the role and management of hyper- and/or hypotension during hemodialysis that needs to be addressed. Objective. To critically review the available published data on the atypical role of hyper- and/or hypotension in cardiovascular associated morbidity and mortality in patients on hemodialysis and to understand the discrepancies in this context. Methods. A comprehensive search of literature employing electronic as well as manual sources and screening 2783 papers published between Jan 1980 and Oct 2015 was conducted to collect, identify, and analyze relevant information through peer-reviewed research articles, systematic reviews, and other published works. The cardiovascular events, including accelerated atherosclerotic cardiovascular disease (ASCVD), stroke, heart failure, myocardial infarction, myocardial ischemia, and stress induced myocardial dysfunction, leading to death were considered relevant. Results. A total of 23 published articles met the inclusion criteria and were included for in-depth review and analysis to finalize a comprehensive systematic review article. All the studies showed a significant association between the blood pressure and cardiovascular disease events in hemodialysis patients. Conclusions. Both intradialytic hypertension/hypotension episodes are major risk factors for cardiovascular mortality with a high percentage of probable causality; however, clinicians are faced with a dilemma on how to evaluate blood pressure and treat this condition.

Polymer-based drug delivery: the quest for local targeting of inflamed intestinal mucosa

Abstract Colon-specific drug delivery has found important applications in the wide array of diseases affecting the lower intestinal tract. Recent developments and advancements in the polymer-based colonic delivery ensure targeted therapeutics with reduced systemic adverse effects. Latest progress in the understanding of polymer science has decorated a polymer-based formulation with a number of special features, which may prove effective in the localized drug targeting at specific sites of the intestine. Upon oral administration, polymeric vehicles or polymer-coated formulations serve to protect the drug from premature release and degradation in the upper gastrointestinal tract. Moreover, it also facilitates the selective accumulation and controlled release of the drug at inflamed sites of the colon. This review article focuses on a wide coverage of major polymers, their modifications, pros and cons, mechanism of colon targeting and applications as a vehicle system for colonic drug delivery, with a special emphasis on the inflammatory bowel disease.

RBBP8 syndrome with microcephaly, intellectual disability, short stature and brachydactyly

Primary microcephaly is clinically variable and genetically heterogeneous. Four phenotypically distinct types of autosomal recessive microcephaly syndromes are due to different RBBP8 mutations. We report on a consanguineous Pakistani family with homozygous RBBP8 mutation c.1808_1809delTA (p.Ile603Lysfs*7) manifesting microcephaly and a distinct combination of skeletal, limb and ectodermal defects, mild intellectual disability, minor facial anomalies, anonychia, disproportionate short stature and brachydactyly, and additionally talipes in one patient.

Adiponectin homolog novel osmotin protects obesity/diabetes-induced NAFLD by upregulating AdipoRs/PPARα signaling in ob/ob and db/db transgenic mouse models

BACKGROUNDnIn metabolic disorders, adiponectin and adiponectin receptors (AdipoR1/R2) signaling has a key role in improving nonalcoholic fatty liver disease (NAFLD) in obesity-associated diabetes.nnnOBJECTIVEnTo the best of our knowledge, here, we reported for the first time the underlying mechanistic therapeutic efficacy of the novel osmotin, a homolog of mammalian adiponectin, against NAFLD in leptin-deficient ob/ob and db/db mice.nnnMETHODSnThe ob/ob and db/db mice were treated with osmotin at a dose of 5u202fμg/g three times a week for two weeks. To co-relate the in vivo results we used the human liver carcinoma HepG2 cells, subjected to knockdown with small siRNAs of AdipoR1/R2 and PPARα genes and treated with osmotin and palmitic acid (P.A.). MTT assay, Western blotting, immunohistofluorescence assays, and plasma biochemical analyses were applied.nnnRESULTSnOsmotin stimulated AdipoR1/R2 and its downstream APPL1/PPAR-α/AMPK/SIRT1 pathways in ob/ob and db/db mice, and HepG2 cells exposed to P.A. Mechanistically, we confirmed that knockdown of AdipoR1/R2 and PPARα by their respective siRNAs abolished the osmotin activity in HepG2 cells exposed to P.A. Overall, the in vivo and in vitro results suggested that osmotin protected against NAFLD through activation of AdipoR1/R2 and its downstream APPL1/PPAR-α/AMPK/SIRT1 pathways as shown by the reduced body weight, blood glucose level and glycated hemoglobin, improved glucose tolerance, attenuated insulin resistance and hepatic glucogenesis, regulated serum lipid parameters, and increased fatty acid oxidation and mitochondrial functions.nnnCONCLUSIONnOur findings strongly suggest that novel osmotin might be a potential novel therapeutic tool against obesity/diabetes-induced NAFLD and other metabolic disorders.

Evaluation of factors affecting time to achieve dry weight among hemodialysis patients using bioimpedance spectroscopy

BackgroundAchieving and maintaining dry weight appears to be an effective strategy for controlling and maintaining normotension among hypertensive patients on hemodialysis (HD).ObjectiveThe present study aimed to determine the time at which the majority of patients achieve postdialysis dry weight using bioimpedance spectroscopy (BIS).MethodsA total of 220 HD patients were prospectively assessed for fluid overload using the Fresenius body composition monitor (BCM). BCM readings were taken at 30 and 45xa0min postdialysis.ResultsAmong the 220 patients included in this study, 120 (54.5%) achieved a euvolemic state at 30xa0min, and 25 (11.4%) achieved it at 45xa0min according to the BCM. In the multivariate analysis, vascular access other than arteriovenous fistula (AVF) (ORu2009=u20090.286, p valueu2009=u20090.049) and cardiovascular disease (ORu2009=u20090.384, p valueu2009=u20090.026) had a statistically significant negative association and receiving HD at Hospital Universiti Sains Malaysia (HUSM) (ORu2009=u20092.705, p valueu2009=u20090.008) had a statistically significant positive association with achieving a euvolemic state at 30xa0min.ConclusionThis suggests that assessing the hydration status at 45xa0min postdialysis in all patients or in those with identified risk factors for not achieving a euvolemic state at 30xa0min will provide a relatively accurate assessment for most patients.

Effect of socio-demographic factors on endogenous biomarkers (cystatin C and creatinine) among elderly chronic kidney disease patients: a cross-sectional study

PurposeCreatinine is normally used to evaluate kidney function among elderly patients in clinical practice, which has been reported to be affected by socio-demographic factors like BMI and age. Cystatin C a newly introduced biomarker may be more efficient in identifying kidney function in obese and aged CKD patients. The aim of the current study was to assess the effect of BMI on endogenous biomarkers (cystatin C and creatinine) among elderly CKD patients in Malaysia, a first such study in the country.MethodsThe current study was conducted at the Hospital University Sains Malaysia, Kelantan. A total of 300 elderly Malay participants ≥u200965xa0years, with CKD, were taken in study. Demographic data, blood pressure, weight, and height were documented. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe Method), while serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader.ResultsThe study participants were divided into three groups on the basis of age. There was a statistically significant difference at the p valueu2009<u20090.05 in serum creatinine level for the three age groups [F (2, 297)u2009=u20091.98, p value 0.045]. Patients were divided into four groups on the basis of BMI. The results of one-way ANOVA revealed a statistically significant difference at the p valueu2009<u20090.05 in the mean serum creatinine level for the four groups [F (3, 396)u2009=u20092.99, p value 0.032]. However, no statistically significant differences between mean serum cystatin C levels were observed on the basis of patient’s age and BMI.ConclusionCystatin C is not related to BMI and age among elderly chronic kidney disease patients. The study clearly evaluates the role of serum cystatin C as a good competitor of creatinine among the elderly CKD patients.