Formulation Design and Pharmaceutical Considerations for Paediatric Patients: Current Status and Future Dimensions

Present day’s conventional pediatrics doses forms are not very attractive towards the children. Due to various reasons such as larger size, bitter taste etc. pediatrics patients rejects the present conventional doses form in many cases. So, there is need for development of some attractive and effective dosage form for children. Present day’s conventional pediatrics doses forms are not very attractive towards the children. Due to various reasons such as larger size, bitter taste etc. pediatrics patients rejects the present conventional doses form in many cases. So there is need for the development of some unconventional dosage forms that proves to be attractive towards the paediatrics populations. This review provides possible advantages and disadvantages of the present conventional dosage forms available for children. Hence present review introduces to various alternatives and unconventional dosage forms viz. effervescent granules / tablets, oral disintegrating tablets and medicated candies and their advantages and disadvantages. Keywords: Effervescent granules, effervescent tab, medicated candy, Oral disintegrating tablet and pediatrics

Formulation and Evaluation of Novel Herbal Formulations Incorporated with Amla Extract for Improved Stability

The objective of the present study was to formulate effervescent and fast dispersible granules by incorporating the fruit extract of Emblica officinalis as an alternate of liquid herbal juices available in market. Amla juice was extracted manually and then subjected to preliminary phytochemical screening which indicates the presence of alkaloids, glycosides, flavonoids, carbohydrates, phenolic compounds, proteins and phytosterols. Lyophilized amla powder was used to formulate effervescent and fast dispersible granules which were further optimized on the basis of concentration of superdisintegrants and effervescent producing agents like croscarmellose sodium, sodium starch glycolate, sodium bicarbonate and citric acid. Powdered formulations were then evaluated on basis of their flow properties like angle of repose, bulk density, tapped density, carr’s index, hausner’s ratio, effervescent cessation time and disintegration time. Among all the effervescent formulations F2 was found to be optimum as it was having least disintegration time of 22 seconds and showed excellent flow properties. In case of the fast dispersible formulations the optimum strength were shown by formulations F9 having croscarmellose with least disintegration time of 52 seconds. Total phenolic content of fresh amla juice were found to be 8.94 mg GAE/100 gm and estimation of ascorbic acid and gallic acid in lyophilized amla powder and developed formulations was carried out by HPTLC. In vitro antioxidant activity of lyophilized amla powder was evaluated by DPPH radical scavenging assay. IC50 value of lyophilized amla powder was found to be 32 ± 0.25 ug/ml calculated in comparison to standard ascorbic acid possessing IC50 value of 25.80 ± 0.2 ug/ml.  Results of present study reveals that developed formulations may serve as alternate product with better quality, consistency and stability in comparison to available herbal liquid formulations. Keywords: Anti-oxidant, Dispersible granules, Effervescent granules, Emblica officinalis

and Validation of Hptlc Method for the Simultaneous Estimation of Ascorbic Acid and Gallic Acid in Amla Juice Preparation

The aim of this study was to asses a simple, selective, precise, and reproducible high performance thin-layer chromatography (HPTLC) method for the simultaneous estimation analysis of ascorbic acid (AA) and gallic acid (GA) in amla juice preparation. The aluminium-based pre-coated TLC plates (Silica gel G 60F 254) were used for the HPTLC fingerprinting analysis. The chromatograms of samples were developed in twin trough glass chamber pre-saturated with mobile phase (toluene: ethyl acetate: methanol: formic acid; 3:3:2:1, v/v/v/v) at room temperature (25 ± 2°C). The densitometric analysis was carried out in absorbance mode at 254 nm. The optimized mobile phase showed compact spots of AA and GA at 0.59 and 0.86 Rf respectively. The linear regression analysis data for the calibration plots of AA and GA showed good linearity (r2= 0.992 and 0.996 respectively) with respect to peak area in the range of 200-1400 ng/spot. The method was validated as per International Conference on Harmonization (ICH) guidelines. The limits of detection and quantification (40 and 140 ng/spot, respectively) were also established. The proposed method has shown the excellent recovery (98.97–99.89%), which supports the suitability of the method for the analysis of AA and GA in the amla juice and other preparations containing these ingredients. Keywords: Amla juice, Ascorbic acid, Gallic acid, HPTLC, ICH guidelines, Validation

SMYD3 represses tumor-intrinsic interferon response in HPV-negative squamous cell carcinoma of the head and neck

Summary: Cancers often display immune escape, but the mechanisms are incompletely understood. Herein, we identify SMYD3 as a mediator of immune escape in human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor response to immunotherapy with pembrolizumab. SMYD3 depletion induces upregulation of multiple type I interferon (IFN) response and antigen presentation machinery genes in HNSCC cells. Mechanistically, SMYD3 binds to and regulates the transcription of UHRF1, encoding for a reader of H3K9me3, which binds to H3K9me3-enriched promoters of key immune-related genes, recruits DNMT1, and silences their expression. SMYD3 further maintains the repression of immune-related genes through intragenic deposition of H4K20me3. In vivo, Smyd3 depletion induces influx of CD8+ T cells and increases sensitivity to anti-programmed death 1 (PD-1) therapy. SMYD3 overexpression is associated with decreased CD8 T cell infiltration and poor response to neoadjuvant pembrolizumab. These data support combining SMYD3 depletion strategies with checkpoint blockade to overcome anti-PD-1 resistance in HPV-negative HNSCC