With the advancement in the field of chronobiology, modern drug delivery approaches have been elevated to a new concept of chronopharmacology, that is, the ability to deliver the therapeutic agent to a patient in a staggered profile. The mammalian circadian pacemaker resides in the paired suprachiasmatic nuclei and influences a multitude of biological processes, including the sleep-wake rhythm. Clock genes are the genes that control the circadian rhythms in physiology and behavior. Twenty-four hours rhythms are demonstrated for the function of physiology and the pathophysiology of diseases. The effectiveness and toxicity of many drugs vary depending on the dosing time. Such chronopharmacological phenomena are influenced by not only the pharmacodynamics, but also the pharmacokinetics of medications. The underlying mechanisms are associated with the 24-hour rhythms of biochemical, physiological, and behavioral processes under the control of the circadian clock. New technology for delivering medications precisely in a time-modulated fashion, by bedside or ambulatory pumps, is being developed to manage human diseases. From the point of view of pharmaceutics, the application of a biological rhythm to pharmacotherapy may be accomplished by the appropriate timing of conventionally formulated tablets and capsules, and a special drug delivery system, to synchronize the drug concentrations with the rhythms in the disease activity. Therefore, the present article gives an overview of the dosing time-dependent alterations in the therapeutic outcome and safety of the drug. The underlying mechanisms and usefulness are introduced from the point of view of chronopharmacology and chronotherapy.

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The purpose of the present work was to develop an optimized immediate release tablet for hypertensive patients using amlodipine besylate as a model drug candidate by optimization technique to produce the intended benefits. A 3 ² factorial design was employed in formulating immediate release tablet. The independent variables selected were superdisintegrants such as sodium starch glycolate and in addition to that, effect of microcrystalline cellulose was studied. The dependent variables considered for study was DT and DP ₆₀ . The tablets prepared were evaluated for thickness, uniformity of weight, hardness, friability, wetting time, in vitro disintegration time, and in vitro drug release study. The response surface plots differentiate the results between the independent and dependent variables. Apart from fulfilling all official and other specifications, the tablets exhibited higher rate of release.

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The purpose of this work was to evaluate the effect of the extraction process and the potential of okra gum as a suspending agent in pharmaceutical oral formulations containing acetaminophen as a model drug. Clarified mucilage of dried okra was either extracted directly with ethanol 96% (F1) or was first treated with base (F2), acid (F3) or heating in the presence of salt (F4) before extraction with ethanol 96%. The samples were used at 0.5% w/v as suspending agents in acetaminophen acetaminophen suspension to deliver 125 mg/5 mL acetaminophen. A binary mixture of F2 and F4 (1:1) was also used. Similar suspensions of acetaminophen containing either hydroxymethylpropylcellulose (HPMC) or tragacanth gum (TRAGA) were produced. Some physicochemical properties of the formulations were evaluated. The rheological properties of acetaminophen-containing treated okra gums (F2-F5) were generally similar. Changes in viscosity with storage were slower in the F2-F5 formulations as compared with F1. Particle size and particle size distribution were different for all formulations, and hysteresis was a function of time and the suspending agent used. The re-dispersion time of the formulations with treated okra gums was generally shorter than that observed with the untreated okra gum. The use of a binary mixture of F2 and F4 resulted in different physicochemical properties from those of either F2 or F4. The physicochemical properties of the formulations were comparable to those with HPMC and TRAGA. It can thus be concluded that treating okra gum with acid, base or salt impacted better physicochemical properties on an acetaminophen pediatric suspension when they were used as suspending agents.

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An investigation was conducted to evaluate the influence of different penetration enhancers in various concentrations on the release of diclofenac sodium (DFS) as a water-soluble drug from Cellulose acetate phthalate polymeric films containing 50% w/w PEG 600 as plasticizer, to choose the most appropriate enhancer and its optimum concentration to be used to achieve the maximum release and permeation of the drug. The addition of various enhancers, as isopropylmyristate (IPM; 0.2_5% w/w), oleic acid (OA; 0.2_5% w/w) and linoleic acid (LOA; 0.2_5% w/w), Tween 80 (T80;1_10% w/w) and transcutol, (TC; 1_10% w/w) enhanced the DFS release from the polymeric films. The enhancement ratio of the penetration enhancers used in the formulation of DFS were found to increase in the order of IPM>LOA>OA>T80>TC. (56.2, 54.1, 50, 48.7 and 48%, respectively). In vitro permeation studies were performed using rabbit abdominal skin as the permeating membrane. The results indicated that maximum permeation was obtained at 24hrs (0.5% IPM, 0.2% LOA, 1% OA, 0.5% T80 and 10% TC, increased skin permeation of DFS by 4.46, 4.06, 3.37, 1.65 and 1.49 time, respectively). IPM was found to be the most efficient enhancer. The results obtained from ANOVA test indicate that the difference in drug permeation rates is highly significant compared to the control formulation (P<0.05). The mechanism of drug release from the polymeric films obey Higuchi's model.

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Buccoadhesives have long been employed to improve the bioavailability of drugs undergoing significant hepatic first pass metabolism. Domperidone is also reported to have low oral bioavailability due to an extensive hepatic first-pass effect. Buccoadhesive hydrophilic matrices containing Domperidone were prepared using a 3² factorial design. The amounts of Carbopol 934P (CP) and Methocel K100LV (HPMC) were taken as the formulation variables (factors) for optimizing bioadhesion and kinetics of dissolution. A mathematical model was generated for each response parameter. Bioadhesive strength tended to vary quite linearly in an increasing order with an increasing amount of each polymer. The drug release pattern for all the formulation combinations was found to be non Fickian, approaching zero-order kinetics. A suitable combination of two polymers provided adequate bioadhesive strength and fairly regulated the release profile up to 4 hr. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results were found to be in close agreement with the experimental findings.

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In the present study cylindrical poly(epsilon-caprolactone) (PCL)-based biodegradable polymeric tamoxifen citrate-loaded subdermal implants were prepared by laboratory-based modified melt extrusion technique. The prepared implants were evaluated for their physicochemical parameters. Drug content in implants by high-performance liquid chromatographic (HPLC) method, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscope (SEM) studies of tamoxifen citrate-loaded implants. Determination of in vitro hydrolytic degradation of polymeric and tamoxifen citrate-loaded implants and in vitro drug release was carried out by using indigenously developed dissolution apparatus. DSC and XRD studies proved that the drug is entrapped in the implant. The highest rate of hydrolytic degradation (weight loss) was observed in blank implants when compared to tamoxifen citrate-loaded implants. The studies proved that the developed method have potential in terms of industrial feasibility.

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A matrix-type transdermal drug delivery system of tamoxifen citrate was developed by using a different ratio of eudragit-RL100, hydroxypropyl methyl cellulose (HPMC-K15), and ethyl cellulose (EC), by the solvent evaporation technique. The effect of the binary mixture of polymers with a penetration enhancer on the physical chemical parameters including, thickness, folding endurance, uniformity of drug content, moisture content, moisture uptake, tensile strength, and in vitro drug permeation were evaluated. The in vitro drug permeation studies were conducted by using modified Keshary-Chein diffusion cells through female Sprague Dawley rat skin using pH 7.4 phosphate buffer saline (PBS). The selected formulation's stability studies were conducted as per the International Conference on Harmonization (ICH) guidelines, and did not show any degradation of the drug.

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Verapamil hydrochloride was formulated as oral-controlled release matrix tablets using hydrophilic polymer such as hydroxypropyl methylcellulose K ₁₅ M (HPMC 15 M) along with electrolytes. In this work a new attempt was made for in situ interactions between drug and electrolytes were devised to control the release of highly water soluble drugs from oral hydrophilic monolithic systems. Electrolytes such as aluminum hydroxide and sodium carbonate were used at different concentrations in various formulations, while drug and polymer concentrations were maintained constantly at 1:2 ratios in all the formulations. These electrolytes were used to monitor matrix swelling and gel properties. Electrolytes at higher concentrations exhibited greater inhibition in drug release from the matrix and low concentrations were accounted for controlled release of the drug. The results indicated that the drug released at a controlled rate were due to differential swelling rate and matrix stiffening, and provides a uniform gel layer. These findings indicated that the swelling and gel formation in the presence of ionizable species within the hydrophilic matrices provide an attractive alternative for controlled drug delivery from a simple monolithic system. Accelerated stability studies were carried out as per ICH guidelines for some selected formulations, which indicated that these formulations were stable at accelerated storage conditions.

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