Vani V

β-Lapachone (β-Lap) is a naturally occurring ortho-naphthoquinone found in the heartwood of Handroanthus impetiginosus and other lapacho trees. The compound has been studied extensively due to its promising anticancer potential in cancer cells with high expression of NAD(P)H:quinone oxidoreductase 1 (NQO1). Reduction of β-Lap by NQO1 leads to the formation of a highly unstable hydroquinone intermediate which undergoes oxidation in a futile redox cycle, generating excessive amounts of ROS. The resultant oxidative stress can lead to DNA damage, hyperactivation of PARP1, reduction of NAD+ and ATP levels and cell death in cancer cells. Although β-Lap exhibits promising pharmacological effects, its poor solubility in water, problems with formulation and pharmacokinetics, possible toxic effects associated with dosing and limited therapeutic window limit the clinical applications of the parent compound. Therefore, various modifications of β-Lap structure were performed using the arylamino, alkoxy, thiosemicarbazone, oxime and prodrug strategies. Computer-assisted drug design approaches such as molecular docking, electronic-structure calculation and ADMET predictions serve as additional methods of selection of promising β-Lap derivatives before synthesis and testing. The present review gives a summary of the chemistry, physicochemical properties, SAR, pharmacology, synthetic and computational approaches to β-Lap and its derivatives [1-3,6]. The review was performed on published scientific papers based on β-lapachone, structural derivatives of β-lapachone, anticancer potential, molecular docking, and computational ADMET study. β-Lapachone was taken into account as the main parent compound, and structural derivatives, including arylamino, alkoxy, oxime, thiosemicarbazone, and other groups, were discussed. The computational methods, including molecular docking, were considered for the assessment of the interaction between the ligands and their targets (proteins) involved in the process of cancer development such as NQO1 and Topoisomerase IIα. Binding interactions, docking score, hydrogen bonding, hydrophobic, and π-π interactions were studied according to the reported studies. Besides, the pharmacokinetic and toxicity properties were also evaluated through ADMET prediction to obtain better anticancer agents [1,4,6,7]

The present study is concerned with formulation and evaluation of mucoadhesive buccal patches containing antihypertensive drug i.e. Timolol to avoid the first pass effect and to improve its bioavailability with reduction in dosing frequency and also dose related side effects. The patches were prepared by solvent casting technique with varying concentration of HPMC E15 as polymer and propylene glycol as the plasticizer and evaluate their physicochemical properties, in vitro drug release, moisture absorption, surface pH, mechanical properties, in vitro bio adhesion, and ex vivo drug permeation through porcine buccal membranes from optimized buccal patch. The physicochemical interaction between timolol and polymer was investigated by Fourier transform infrared spectroscopy. Moisture absorption, surface pH, tensile strength, elongation at break, peak detachment force and work of adhesion values of the optimized formulation F4 were found to be 124±10.59%, pH 6.61±0.28, 3.89 kg/mm2, 14.16 mm2, 4.92±0.06N and 0.65±0.08mJ respectively. Formulation F4 showed 68.99 ±1.67% of the drug release in in vitro condition and follows zero order kinetics and drug release mechanism follows non-fickian diffusion. Ex vivo drug permeation through porcine buccal membrane was performed and 58.52±1.59% of the drug permeated in 6 hrs with flux 0.22 mg/h/cm2.The optimized formulation F4 with permeation enhancer tween 80 (1% v/w) showed drug release 64.47±1.63 % in 6 hrs with flux 0.33mg/h/cm2. FTIR studies showed no evidence of interaction between the drug and polymers. Drug release from the buccal patches follows desire controlled release phenomenon as required in mucoadhesive drug delivery.

  The purpose of the present study was to develop an optimized gastric floating extended release matrix tablet of Metformin hydrochloride (FERMTs) using a hydrophilic polymer, HPMC K4M, a hydrophobic polymer ethyl cellulose and sodium bicarbonate as buoyancy contributor. The formulation of FERMTs were designed by D-optimal mixture design taking % of HPMC K4M, ethyl cellulose and sodium bicarbonate as formulation variables and prepared by wet granulation method. The FERMTs were then evaluated for hardness, friability, weight variation, content uniformity, in vitro drug release and floating capacity. Finally, the floating lag time (FLT) and cumulative % drug release at 1h, 2h, 6h and 10h were taken as response variables and the FERMT formulation was numerically optimized by D-optimal mixture design using Design-Expert software (version 8.1). The optimized formula showed excellent floating efficiency over 10 h period with FLT of 9.61 mins. The release profile of optimized formula showed much closed similarity with that of USP reference dissolution profile (f2 value= 87.95). Analysis of dissolution data showed that the kinetic of drug release followed Korsemeyer-Peppas and Higuchi model.