Quality by design-based development and in vitro evaluation of dual release tablet of etoricoxib and thiocolchicoside: A novel chronotherapeutic approach for arthritis pain management

Article

Author: Saini, Geetanjali ; Singh, Supriya ; Sharma, Sanjay ; Singh, Bhupendra ; Choudhary, Deepak ; Sharma, Anchal

OBJECTIVEThe traditional drug delivery system is not much effective when treating chronopathological diseases like arthritis. Consequently, there is a gap in the market for a delivery system that can provide an explicit treatment following the chronopharmacology of this disorder. The present study is based on the objective to develop Eudragit coated dual release bilayer tablet designed by the quality by design (QbD) and based on the chronotherapeutic approach. The dual release tablet contained an immediate release layer of etoricoxib and a sustained release layer of thiocolchicoside.MATERIAL AND METHODThe quality target product profile (QTTP) of the formulation was established along with critical quality attributes (CQA). The optimization of the dual release layer was done using a three-level, three-factor Box-Behnken design. A total of thirteen formulations of etoricoxib (ET1-ET13) and thiocolchicoside (TH1-TH13) were developed based on the design composition of etoricoxib, sodium starch glycolate and sodium bicarbonate for the immediate release (IR) layer and thiocolchicoside, HPMC E5 LV and magnesium stearate for the sustained release (SR) layer respectively. The developed dual release layers were compressed to form a bilayer tablet. The bilayer tablets were further coated with pH-dependent polymer Eudragit S-100 to avoid drug release in upper GIT. The initial characterization and drug-excipient interaction studies were performed initially using infra-red (IR) spectroscopy and X-ray diffraction studies (XRD). Formulations showing good micrometric properties, disintegration and drug release were selected for final compression of bilayer tablets.RESULTFormulation ET13 showed the fastest drug release (88%) at 15minutes and quick disintegration time (21s). The sustained release thiocolchicoside tablet layer (TH1-TH13) had a hardness that varied from 4.01 to 4.45kg/cm². Formulation TH12 had the highest hardness, whereas TH6 showed the lowest hardness. The sustained release layer showing 97.63% of drug release after 8hours was selected for the compression to bilayer tablet. The developed dual layer tablets were investigated for quality parameters like hardness, percentage friability, weight variation, disintegration and dissolution.CONCLUSIONA high level of patient compliance is ensured through the current design as the patient does not need to get out of bed at night to take the medication.

01 Oct 1998·Oral Microbiology and Immunology

Acid‐regulated proteins induced by Streptococcus mutans and other oral bacteria during acid shock

Article

Author: I. R. Hamilton ; G. Svensäter

Our previous research has demonstrated that with the more aciduric oral bacteria, an acid shock to sub‐lethal pH values results in the induction of an acid tolerance response that protects the cells at extremely low pH (pH 3.0–4.0) that kills unadapted control cells maintained at pH 7.5 (Oral Microbiol Immunol 1997: 12: 266–273). In this study, we were interested in comparing the protein profiles of acid‐shocked and control cells of nine organisms from three acid‐ogenic genera that could be categorized as strong, weak and non‐acid responders in an attempt to identify proteins that could be classified as acid‐regulated proteins and which may be important in the process of survival at very low pH. For this, log‐phase cultures were rapidly acidified from pH 7.5 to 5.5 in the presence of [14C]‐amino acids for varying periods up to 2 h, the period previously shown to be required for maximum induction of the acid response. The cells were extracted for total protein and subjected to one‐dimensional sodium dodecyl sulfate‐poly‐acrylamide chromatography with comparable control and acid‐shocked protein profiles compared by scanning and computer analysis. Of particular interest were the proteins in the acid‐shocked cells that showed enhanced labeling (i.e., synthesis) over the control cells, since these were considered acid‐regulated proteins of importance in pH homeostasis. Streptococcus mutans LT11 generated the most rapid and complex pattern: a total of 36 acid‐regulated proteins showing enhanced synthesis, with 25 appearing within the first 30 min of acid shock. The enhanced synthesis was transient with all proteins, with the exception of two with molecular weights of 50/49 and 33/32 kDa. Within the acid‐regulated proteins were proteins having molecular weights comparable to the heat shock proteins and the various subunits of the membrane H+/ATPase. By comparison, the strong responder, Lactobacillus casei 151, showed the enhanced formation of only nine proteins within the first 30 min of the acid shock, with a total of 11 acid‐regulated proteins formed during the 2‐h adaptation period with enhanced synthesis transient for seven of these proteins. Streptococcus salivarius AT2 and Streptococcus gordonii TH12 had the formation of 6 and 8 proteins enhanced, while the weakly responding organisms, Streptococcus sanguis ATCC 10556 and Streptococcus oralis ATCC 10557, exhibited 8 and 6 such proteins, respectively. Even non‐responding strains unable to survive at very low pH, such as Streptococcus sobrinus CH125/43, Streptococcus mitis ATCC 12261 and Actinomyces naeslundii 301‐13 showed the initial formation of 3–9 acid‐regulated proteins, but protein synthesis was not sustained over the entire adaptation period. Clearly, the survival of oral bacteria at very low pH is related, not to the total number of the acid‐regulated proteins induced per se but to the formation of key proteins that function to augment normal pH homeostasis.

PLOS ONEQ3 · CROSS-FIELD

Systemic Resistance to Powdery Mildew in Brassica napus (AACC) and Raphanus alboglabra (RRCC) by Trichoderma harzianum TH12

Q3 · CROSS-FIELD

ArticleOA

Author: Li, Maoteng ; Alkooranee, Jawadayn Talib ; Yin, Yongtai ; Lu, Guangyuan ; Wu, Jiangsheng ; Aledan, Tamarah Raad ; Jiang, Yingfen

Trichoderma harzianum TH12 is a microbial pesticide for certain rapeseed diseases. The mechanism of systemic resistance induced by TH12 or its cell-free culture filtrate (CF) in Brassica napus (AACC) and Raphanus alboglabra (RRCC) to powdery mildew disease caused by ascomycete Erysiphe cruciferarum was investigated. In this study, we conducted the first large-scale global study on the cellular and molecular aspects of B. napus and R. alboglabra infected with E. cruciferarum. The histological study showed the resistance of R. alboglabra to powdery mildew disease. The growth of fungal colonies was not observed on R. alboglabra leaves at 1, 2, 4, 6, 8, and 10 days post-inoculation (dpi), whereas this was clearly observed on B. napus leaves after 6 dpi. In addition, the gene expression of six plant defense-related genes, namely, PR-1, PR-2 (a marker for SA signaling), PR-3, PDF 1.2 (a marker for JA/ET signaling), CHI620, and CHI570, for both genotypes were analyzed in the leaves of B. napus and R. alboglabra after treatment with TH12 or CF and compared with the non-treated ones. The qRT-PCR results showed that the PR-1 and PR-2 expression levels increased in E. cruciferarum-infected leaves, but decreased in the TH12-treated leaves compared with leaves treated with CF. The expression levels of PR-3 and PDF1.2 decreased in plants infected by E. cruciferarum. However, expression levels increased when the leaves were treated with TH12. For the first time, we disclosed the nature of gene expression in B. napus and R. alboglabra to explore the resistance pathways in the leaves of both genotypes infected and non-infected by powdery mildew and inoculated or non-inoculated with elicitor factors. Results suggested that R. alboglabra exhibited resistance to powdery mildew disease, and the application of T. harzianum and its CF are a useful tool to facilitate new protection methods for resist or susceptible plants.

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Pancreatic Cancer	Phase 1	CN	Jinan Taihe Pharmaceutical Technology Co., Ltd.	-
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