Term Stability Studies Research Articles

Actd regulatory requirements for approving an anticancer drug (thioguanine)

This work makes document handling safer and more accessible. It can manage even more complex papers in addition to all the benefits. Using this work, a composite document or papers from several different document sources and formats can be assembled, updated, and published. Each document is treated as a single, identically organized document. BMR, Process Validation Record, Stability Study (including Accelerated & Long Term Stability Study per Myanmar Zone Specification), Anticancer Drug Packing Requirements, and Certificate for Product Permission (covering all aspects from manufacturing to its packing & registration) are among the required documents. It offers reliable scientific methods for determining the effectiveness, safety, and quality of medicinal items. It will assist in comprehending the documentation needs for drug registration in Myanmar.

Gabapentin: An impurity profiling approach with hydrogen peroxide induced thermal oxidation in autoclave

Predicting unconventional pathways in long term stability studies can be very challenging, especially in solid state degradation. This is of vital importance for enhancement in the level of degradation and to further enable the isolation of unknown degradation products. Predicting the mechanism or pathway also help in designing control strategies to minimise the potential chances of impurity formation. In this context, the lagtime of most oxidative degradation mechanisms is extremely important, which allows enough requisite of free radicals etc., one of the unconventional pathways. This is difficult to replicate in degradation studies involving usual solution form. In this investigation, we demonstrate that employing autoclave degradation with hydrogen peroxide conditions provide an enhanced level of an unknown degradation product, which was found to be futile in traditional forced degradation studies. The conditions used probably bypass the lag time. This impurity has been isolated using preparative liquid chromatography (Prep-HPLC) method and spectroscopic techniques like high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance NMR (1H, 13C, DEPT-135, NOESY, APT) for elucidation of the molecular structure. The impurity was identified as a dimer of gabapentin impurity-A (impurity (2,2′-diaza[l,2′-bispiro[4.5]decane]-3,3′-dione) and named it as impurity-U. A plausible mechanism for the formation of isolated impurity is proposed. HPLC methods have been developed and reported for the determination of gabapentin and its related substances using UV detection.

Quantification of Arbortristoside-A isolated from Nyctanthes arbor-tristis using HPLC: Method development and pharmaceutical applications

Arbortristoside-A (Arbor-A) is a naturally occurring iridoid glycoside and herbal-based lead molecule with proven medicinal potential. Aiming at the development of an efficient analytical tool for the quantification of Arbor-A in pharmaceutical dosage forms, in the presented work, we developed an economical, fast, and sensitive RP-HPLC-UV method and validated the procedure as per the ICH guidelines, Q2(R1). The chromatographic separation was accomplished under the optimised experimental conditions using an HPLC system with an LC-2010 autosampler, a PDA detector, and a Phenomenex C18 column with the mobile phase composed of a 70:30 (v/v) water-acetonitrile mixture eluting isocratically at a flow rate of 1 mL/min at ambient temperature, and UV detection at 310 nm. Arbor-A showed a sharp peak at the retention time of 5.60 min and exhibited linearity (R2 = 0.9988) with LOD and LOQ of 0.50 μg/mL and 1.50 μg/mL, respectively. The accuracy of the method was 98.33–101.36 % with acceptable intra-day and inter-day precisions as well as robustness (<2% RSD). To ratify the applicability of the presented approach in emerging pharmaceuticals, a nanoformulation loaded with Arbor-A was designed and analysed utilising the provided methodology. The method has also enabled to determine the degradation kinetics of Arbor-A under stress conditions, etcetera, employing forced degradation and short term stability studies.

Formulation and Evaluation of Mouth Dissolving Loratadine Tablet using Super Disintigrants

The objective of the work was design to improve palatability in orally administered products has prompted the development of formulation with improved performance and acceptability. Mouth-dispersing tablets dissolve or break down in saliva and are ingested without the use of water. Antihistamine loratadine is primarily used to treat hay fever, allergies, itchy eyes, and hives symptoms. It functions by obstructing histamine, which the body releases after an allergic reaction. The objective of the current study was to use the physical mixing approach to increase the solubility and dissolving rate using Croscarmellose sodium. From FIIR identification of drug is done and followed by physicochemical parameters. Determination of drug polymer incompatibility is by FTIR method. Loratadine MDT were prepared by using different superdisintegrants as Croscarmellose sodium, Orange peel pectine and Hibiscus mucilage by direct compression method. Only the physiochemical characterization, formulation, and in-vitro assessment of Loratadine mouthwash pills were carried out in this study. In addition to in-vitro research, in-vivo drug studies are crucial . Future in-vivo research is vital to establish the in-vitro in-vivo correlation that is required for the development of successful formulations and also long term stability studies.

Rationally designed oxygen vacant TiO2 decorated with covalent organic framework for enhanced electrocatalytic nitrogen reduction to ammonia

This study focuses on the rational design of uniformly distributed oxygen vacant TiO2−x nanoparticles supported on an anthraquinone-based covalent organic framework (TiO2−x@COF-Aq), aiming to address the challenges of Haber-Bosch process. The N-philic nature of Ti and the presence of abundant oxygen vacant sites on the TiO2−x@COF-Aq promote the adsorption of nitrogen, facilitating the electrocatalytic NRR process. The theoretical study reveals that TiO2−x@COF-Aq suppresses the H+ adsorption, facilitates oxygen vacancy formation and favors the N2 adsorption at oxygen vacant sites. The synthesized nanocatalyst exhibits many folds higher electrochemical NRR activity than bulk oxygen vacant TiO2−x with an ammonia yield of ∼30 μg mg-1 h–1 and ∼16% Faradaic efficiency. Long term stability study manifests the robustness and industrial significance of the catalyst. The overall synergism between the stabilized nanoparticle and functionalized COF has established the fundamental understanding of the proton coupled electron transfer for N2 fixation through experiments and theoretical findings.

Development and characterization of self-micro emulsifying drug delivery system of cilnidipine using simplex centroid mixture design

Objective: The main objective of the current research work was development and characterization of self-micro emulsifying drug delivery system of cilnidipine which is poorly water soluble drug. The improved solubility could offer improved dissolution as well as oral bioavailability. Method: Component excipients were selected based on the preliminary studies, capryol 90 and triacetin (1:1) selected as an oil, tween 80 selected as surfactant, transcutol p selected as co-surfactant based on the maximum solubility and better emulsification efficiency. The ternary phase diagram was constructed to identify the optimum composition of the formulation. Simplex centroid mixture design was applied for selection of optimized batch of SMEDDS. Capryol 90 and triacetin, tween 80 and transcutol p were taken as an independent variables X1, X2 &amp; X3 respectively, while emulsification time (Y1) and % drug release at 2 minute (Y2) were taken as dependent variables. Optimized SMEDDS was evaluated based on % transmittance, emulsification time, globule size, PDI, % drug release, and cloud point. After that, SMEDDS were filled in capsule and short term stability study was done and SMEDDS compared with pure drug for dissolution profile. Result and discussion: Optimized batch containing capryol 90 and triacetin (1:1), tween 80 and transcutol p at a concentration of 10%, 67% and 23% respectively. The solubility of cilnidipine is increased by using capryol 90 and triacetin (1:1) as an oily phase. All the evaluation parameters of the optimized SMEDDS were met the acceptance criteria. Optimized batch of SMEDDS showed &gt; 90% drug release within 2 minutes. Dissolution was improved as compared to the pure drug. Conclusion: A self-micro emulsifying drug delivery system of cilnidipine was developed successfully. Present work demonstrated for improving the dissolution of cilnidipine. This may lead to improved oral bioavailability of cilnidipine for the treatment of hypertension.

The polymorph landscape of dabigatran etexilate mesylate: Taking the challenge to bring a metastable polymorph to market

Dabigatran etexilate mesylate is polymorphic and can exist in different crystalline forms. Two polymorphs have been encountered during the development of this drug substance, namely anhydrous form I and anhydrous form II. Additionally, a hemihydrate was observed, if larger amounts of water were present during crystallization in the salt formation step. Finally, a high temperature form III can be obtained by heating anhydrous form I above 150 °C. All three at room-temperature accessible forms were characterized by means of microscopy, X-ray powder diffraction, thermal analysis, IR- and Raman spectroscopy. In addition, solubility parameters (equilibrium solubility and intrinsic dissolution rate, heat of solution) were collected on all three forms. The crystal structure of all three at room-temperature accessible forms could be obtained using electron diffraction. Anhydrous form I has a monoclinic crystal lattice (C2/c), anhydrous form II a triclinic one (P1¯), and the hemihydrate crystallizes also in a monoclinic space group (P2/c). From the obtained data there is clear evidence that anhydrous form II is thermodynamically more stable than anhydrous form I. Form I and form II are monotropically related to each other indicating that they may coexist over a wide temperature range. The hemihydrate is a completely independent crystalline modification of dabigatran etexilate mesylate. It is another thermodynamically stable form and structurally not related to the two anhydrous forms. The hemihydrate melts at ca. 125 °C, there is no conversion to either anhydrous form I or form II upon dehydration. The high temperature form III is enantiotropically related to form I and only stable above the phase transition temperature at ca. 150 °C and its melting point at ca. 183 °C. The energy difference between anhydrous form I and form II was found to be only 2.5 – 3.0 J/g. Both forms have very similar aqueous solubility characteristics. Although anhydrous form II is the thermodynamically more stable form, anhydrous form I was chosen for development. The selection of form I for development was mainly based on the superior bulk processing properties of anhydrous form I in drug substance synthesis and further drug product processing as well as its slightly better chemically stability in pivotal long term stability studies. Anhydrous form I, although meta stable, is still stable enough that conversion to the more stable form II can occur only to a limited extent during drug substance synthesis and drug product manufacturing. From long term stability data on both bulk drug substance as well as drug product, there is no indication that form I transforms to form II during storage. Even under stress conditions where form I was stored up to 4 weeks at 70 °C, no conversion to form II was observed.

Investigation on Potential of Karanjin Loaded Emulgel for Improved Efficacy against Psoriasis

Abstract: Aim: The objective of this work was to prepare and characterize Karanjin loaded emulgel for enhanced effectiveness against psoriasis. Materials and Methods: Karanjin emulsion was prepared using peppermint oil and was loaded in gel base (carbopol 940 was used as gelling agent). Various batches of emulsion were prepared by varying concentration of tween 80 and were optimized for various parameters. Results: Optimized emulsion (KE5) gave droplet size of 110.4 ± 1.56 nm, -40.9 ± 1.11 mV zeta potential, entrapment efficiency of 92.12 ± 2.8%, and creaming volume of 98.1 ± 0.4 and was found to be stable for 30 days during short term stability studies. The pH and viscosity of optimized Karanjin loaded emulgel was found to be 7.31 and 8060 cp respectively. In-vitro release of Karanjin from optimized emulgel was found to be 95.36% in 6 hr indicating slow release. Ex vivo permeation study in skin indicated 88% permeation of karanjin in 5 hr from optimized emulgel formulation compared to 16.52% permeation from solution formulation. In vivo study showed significant improvement in PASI score upon application of Karanjin loaded emulgel formulation. Conclusion: The results prove potential efficacy of the emulgel formulation in improving efficacy of Karanjin against psoriasis. Keywords: Psoriasis, Emulgel, Karanjin, PASI Scoring, In vivo anti-psoriatic activity, Ex vivo permeation.

Long term stability studies in the presence of crab cavities and high order multipoles in the CERN super proton synchrotron and high luminosity large hadron collider

In 2018 the world’s first Crab Cavity (CC) experiments with protons were successfully performed, aiming to study the CC effect on a proton beam and evaluate the engineering challenges. Before the commencement of these experiments, the impact of the CCs and their multipoles on the long term particle stability of the SPS was studied using dynamic aperture simulations. Furthermore, in order to ensure the long term stability and luminosity performance of the LHC upgrade, the High Luminosity LHC (HL-LHC), the limits of stable motion were also examined in the presence of CC multipole errors, CC voltage errors and additional non-linearities such as the beam–beam effects. This paper presents the comprehensive dynamic aperture results for the SPS and HL-LHC for different CC, accelerator and beam configurations in view of guiding the engineering specifications of the tolerances of the crab cavity multipole errors.

Iron supported on beaded carbon black as active, selective and stable catalyst for direct CO2 to olefin conversion

The Fischer-Tropsch-to-Olefins process allows to convert waste stemming CO2 with green hydrogen to olefins. Iron can catalyse both core reactions: 1) reverse-water-gas-shift as well as 2) Fischer-Tropsch. Carbon supported catalysts were reported to be highly attractive in this context, but until now mainly non technically applicable research carbons like nanotubes or ordered mesoporous carbons were studied and long term stability studies are missing. Here, beaded carbon blacks, were studied as available and inexpensive support materials for Fe catalysts in CO2-based FTO. The most promising support yielded selectivities towards olefins of almost 40% and showed for 170 h high stability.

STEP TOWORDS THE FORMULATION OF INJECTABLE HYDROGEL: PREFORMULATION STUDIES OF TERIFLUNOMIDE

Purpose: The aim of formulation of this hydrogel is to treat the osteoarthritis which is one of the common inflammatory autoimmune disorders of joints. The use of conventional drugs like NSAIDs having various side effects.&#x0D; The aim of our research was to develop a formulation of injectable hydrogel containing teriflunomide. This study will be helps us for the development of stable, robust and therapeutically effective dosage form.&#x0D; Method: Solubility of Teriflunomaide was determined by using various solvents. By using infrared spectrum and absorption maxima the purity of sample was checked. With the help of UV spectrophotometer standard UV curve was developed. Drug excipients compatibility studies were performed using Fourier transform infrared spectroscopy, differential scanning colorimetry, partition coefficient and also short term drug solution stability studies were performed.&#x0D; Result: Teriflunomide is soluble in methanol &amp; 0.1 N NaOH on the other hand poorly soluble in distilled water, phosphate buffer (pH 7.4) and 0.1 N HCl. Absorption maxima was observed at 292nm and infrared spectrum was showing the characteristic peaks. The standard curve obtained was linear with correlation coefficient below 1. Log P value obtained at 2.78 it confirms that teriflunomide is having both hydrophilic &amp; hydrophobic nature. After the entire short term stability studies drug was found to be stable in short term stability studies.&#x0D; Conclusion: The studies like melting point, FTIR etc suggested that drug selected for the formulation was found to be pure. Partition coefficient values suggested that it is having both hydrophilic and hydrophobic nature. Results obtained from short term stability studies were suggested that drug is stable showing no degradation on phosphate buffer which confirmed by no shift of λ max.

Trace Aldehydes in Solid Oral Dosage Forms as Catalysts for Nitrosating Secondary Amines

Nitrosamine impurities may form during drug substance manufacturing processes. Here, we focus on nitrosamine impurity level growth in oral drug products during long term stability studies. Nitrosamine growth mechanisms in oral dosage forms are typically framed as due to nitrosating agents that can be formed in solutions of nitrous acid with a required pH value of around pH 5 or below. We strive in this work to bring awareness to pharmaceutical scientists that formaldehyde, common in oral dosage form excipients, has previously been shown in solution to catalyze the reaction between secondary amines and nitrite ion to give nitrosamine products. This mechanism operates at pH ∼6 and higher. We attempt to re-frame the solution work as relevant to pharmaceutical solid dosage forms. Recent examples of solid dosage form product recalls are used to demonstrate the formaldehyde catalyzed nitrosation pathway operating in the solid state.

Bioanalytical Method Development, Validation and Stability Assessment of Xanthohumol in Rat Plasma.

Xanthohumol (XH) a prenylated chalcone has diverse therapeutic effects against various diseases. In the present study, a bioanalytical method was developed for XH in rat plasma using reverse phase high performance liquid chromatography. The validation of the method was performed as per ICH M10 guidelines using curcumin as an internal standard. The Isocratic elution method was used with a run time of 10 min, wherein the mobile phase ratio 0.1% v/v OPA (A): Methanol (B) was 15:85 v/v at flow rate 0.8 mL/min and injection volume of 20 µL. The chromatograms of XH and curcumin was recorded at a wavelength of 370 nm. The retention time for XH and curcumin was 7.4 and 5.8 min, respectively. The spiked XH from plasma was extracted by the protein precipitation method. The developed method was linear with R2 value of 0.9996 over a concentration range of 50–250 ng/mL along with LLOQ. The results of all the validation parameters are found to be within the accepted limits with %RSD value less than 2 and the percentage recovery was found to be greater than 95%. Based on the %RSD and percentage recovery results it was confirmed that the method was precise and accurate among the study replicates. LOD and LOQ values in plasma samples were found to be 8.49 ng/mL and 25.73 ng/mL, respectively. The stability studies like freeze thaw, short term and long-term stability studies were also performed, %RSD and percentage recovery of the XH from plasma samples were within the acceptable limits. Therefore, the developed bioanalytical method can be used effectively for estimation of XH in plasma samples.

Corneal targeted fenticonazole nitrate-loaded novasomes for the management of ocular candidiasis: Preparation, in vitro characterization, ex vivo and in vivo assessments

The purpose of this manuscript was to develop and optimize Fenticonazole Nitrate (FTN)-loaded novasomes aiming to enhance drug corneal penetration and to improve its antifungal activity. Ethanol injection was used to formulate FTN-loaded novasomes adopting a central composite design. The researched factors were: stearic acid concentration (g%) (A), span 80: drug ratio (B) and cholesterol amount (mg) (C), and their effects on percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP), and in vitro drug release after 8 hours (Q8h) were studied. Numerical optimization by Design-Expert® software was employed to select the optimum formula in respect to highest EE%, ZP (as absolute value), and Q8h >80% and lowest PS and PDI. Additional evaluation of the optimum formula was accomplished by short term stability study, effect of gamma sterilization, determination of Minimal Inhibitory Concentration and ex vivo corneal permeation study. The in vivo evaluation of the optimum formula was done to ensure its safety via in vivo ocular irritancy and in vivo corneal tolerance studies. Also, the efficacy was confirmed through in vivo corneal uptake study and susceptibility test. The optimum formula with the highest desirability value (0.738) showed EE% (94.31%), PS (197.05 nm), ZP (-66.95 mV) and Q8h (85.33%). It revealed to be safe, with augmented corneal permeation (527.98 µg/cm2) that leads to higher antifungal activity. The above results confirmed the validity of novasomes to improve the corneal permeation and antifungal activity of Fenticonazole Nitrate.

Stable Solid Dispersion Incorporated Sustained Release Oral Gel of 23 mg Donepezil Hcl

The objective of the present study is to formulate and evaluate stable solid dispersion incorporated sustained release oral gel of donepezil Hcl. Solid dispersions were prepared using HPMC K100M and stearic acid using physical mixture, co-grinding and fusion methods and incorporated into the previously prepared gel bases using sodium CMC and sodium alginate and suitable formulation was optimised. All the formulations were subjected to physicochemical evaluation parameters. Solid dispersions of donepezil were prepared with HPMC K100 and stearic acid by using different methods like physical mixtures, co grinding and fusion method in the ratios of 1:1, 1:2 and 1:3. From the invitro dissolution studies, it was found that SD made by co grinding and fusion method showed sustained release and were selected and incorporated into the gel formulations made of SCMC 4% and sodium alginate 4%. The release studies of solid dispersion incorporated gel SD-HPMC K100M showed (SDG1) 87.55% and (SDG2) 88.9% at 8th hour and SD-stearic acid showed (SDG3) 83.26% and (SDG4) 82.57% at 8th hour. It was concluded that stearic acid solid dispersions incorporated in sodium CMC gels (SDG3) were optimised using short term stability studies with no leakage of drug in comparison to solid dispersions of HPMC K100M in sodium CMC gel l. Physico-chemical evaluation parameters were carried out for optimised formulations and found to be within limits. The optimized SD incorporated gel formulation of donepezil can be an alternative to SR tablet in improving the compliance of the geriatric patients.

Formulation, Optimization and Evaluation of Ticagrelor Loaded Self Microemulsifying Chewable Tablets

Abstract: Ticagrelor is a new generation Adenosine diphosphate receptor inhibitor drug which is highly lipohilic having poor aqueous solubility used in the treatment of Acute Coronary Syndrome and prevention of Thrombotic events like Stroke and Heart Attack. An approach has been made to develop Chewable tablets of drug loaded on Self-microemulsifying drug delivery systems (SMEDDS), screen suitable adsorbent for solidification of formulated SMEDDS and to study the effect of superdisintegrants in chewable tablets. Methods: On basis of Pseudoternary diagrams constructed for selected oil, surfactant and cosurfactant, SMEDDS formulation was formulated using Capmul MCM EP oil with surfactant (Cremophor RH 40) and co-surfactant (PEG 400) which was solidified using selected adsorbent. Chewable tablets were compressed by direct compression method using superdisintegrants. Results: IR Studies and DSC studies revealed compatibility and stability of drug in formulation. Compression blend containing Solidified SMEDDS possessed good flow and compressibility. Chewable tablets compressed using Soy Polysaccharides as super disintegrant showed least wetting and disintegration time, drug release of 97.68% within 30 min. Short term stability studies revealed no significant change in physical and chemical properties. Conclusion: These results suggest that the Ticagrelor loaded self microemulsifying chewable tablets can be a promising oral drug delivery system to improve the solubility and dissolution profile of Ticagrelor. Key words: Ticagrelor, SMEDDS, Adsorbents, Chewable tablets, Acute coronary syndrome.

Formulation, optimization and validation of floating oral in situ gel of Ivabradine hydrochloride.

Aim: Ivabradine hydrochloride is a hyperpolarized activated channel blocker used for symptomatic treatment of chronic angina pectoris. However, due to its short half-life it is rapidly eliminated from systemic circulation. Materials & methods: Floating in situ gel was formulated using sodium alginate and HPMC K 100M by pH induced ion gelation technique employing 32 factorial design for optimization and evaluated. Results: The in situ formulation remained buoyant in gastric environment for 12h. Optimized formulation sustained and prolonged drug release in comparison withmarketed product. Kinetic analysis of drug release indicated non fickian mechanism. Short term stability studies showed no significant changes indicating good formulation stability. Conclusion: Formulated in situ solution shows potential effective sustained release over a prolonged period of time.

FORMULATION AND IN VITRO EVALUATION OF CHITOSAN FILMS CONTAINING LINEZOLID FOR THE TREATMENT OF PERIODONTITIS

The study was aimed to formulate a dental film containing linezolid, a broad spectrum antimicrobial agent which could be easily placed into the periodontal pocket and be capable of delivering therapeutic concentrations of drug for prolonged periods and also reducing the side effects. In the present investigation, chitosan strips containing linezolid in three different concentrations (10, 20, and 30 %w/w with respect to the weight of polymer) were prepared by the solvent casting method, by using 1 %V/V acetic acid solution. The prepared formulations were evaluated for various properties such as weight variation, thickness, folding endurance, moisture loss, tensile strength, in vitro release, release kinetic study and stability studies. The weight variation and thickness were found to be in the range of (0.99-1.58 mg) and (0.92-1.76 mm), the moisture content, folding endurance was found to be maximum for the plain film and minimum for the drug containing formulation. The tensile strength was found to be in the range of (2.44-1.43 kg/ mm2 ) for the formulation. The dissolution studies showed a burst release initially followed by a progressive fall in the release of the drug (91.15 - 95.87 %) and the release kinetics followed the zero-order pattern. The short term stability studies were conducted and there were no significant changes observed. Hence, low dose, site-specific linezolid film is a potential tool for the treatment of periodontitis.

BIO-ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS ESTIMATION OF DECITABINE AND CEDAZURIDINE IN HUMAN PLASMA USING LC-MS/MS

Objective: The present work aimed to develop a novel, reliable and accurate Liquid Chromatography-Mass Spectrometry/Mass spectrometry (LC-MS/MS) method for the simultaneous quantification of Decitabine and Cedazuridine a combined medication used for the treatment of chronic myelomonocytic leukemia in human plasma. Methods: Talazoparib drug is used as an internal standard in the study. Both the analytes and internal standard were isolated from 100 ml plasma samples by liquid-liquid extraction and then chromatographed on Zorbax SB-CN (4.6 mm×75 mm, 3.5 µm) column with a mobile phase consisting of 0.1 % ammonium formate and methanol in the ratio of 65:45 (v/v) pumped at 0.5 ml/min. The method had a chromatographic total run time of 5 min. Results: The developed method gave a symmetric peak at a retention time of 1.7 min for Decitabine, 2.2 min for Cedazuridine, 3.5 min for Talazoparib and satisfied all the peak properties as per USP guidelines. The mass spectral characterization of separated analytes in the LC method was performed using a mass detector operated at Multiple Reaction Monitoring mode with precursor-to-product ion transitions at m/z of 229 to m/z of 114 as MH+ion for Decitabine, m/z of 269 to m/z of 118 as MH+ion for Cedazuridine. A very sensitive limit of detection of 0.3 ng/ml was observed and showed a calibration curve linear over the concentration range of LLOQ (lower limit of quantification) to 500 ng/ml. The other validation parameters were found to have acceptable accuracy, precision, linearity, and selectivity. The mean extraction concentration was acceptable and very high for both the analytes in HQC (high-quality control concentration), MQC (medium quality control concentration) and LLOQ levels. The peak area response ratio of Decitabine and Cedazuridine with the internal standard in freeze-thaw, short term and long term stability studies was found to be acceptable confirms that the method is stable. Conclusion: It can be concluded that the proposed method is specific, accurate, and precise and could be used for the simultaneous estimation of Decitabine and Cedazuridine in human plasma.

Improved Efficacy and Stability of Silymarin Loaded Nanocochleates Over Liposomes for the Treatment of Skin Diseases

Aim: Silymarin, a complex polyphenolic component mixture with anti-oxidant, anti-inflammatory, and membrane-stabilizing property is being investigated in several dermatological conditions. Present research aims to evaluate potential of silymarin loaded nanocochleates and liposomal topical application for treating chronic skin diseases.&#x0D; Study Design: Silymarin loaded liposomes and nanocochleates were formulated and optimized using Design Expert software. Different invitro and exvivo tests were performed to compare their performance.&#x0D; Place and Duration of Study: The study was conducted in Smt. Kashibai Navale College of Pharmacy, Pune, India, between January 2019 till February 2020.&#x0D; Methodology: Liposomes were prepared using ethanol injection method and further treated with calcium chloride to form nanocochleates by trapping method. Design of experiments (32 Factorial Design) was used for optimization of nanocochleates. Cell line studies (HaCaT cell lines) and short term stability studies were performed to compare the efficacy and stability respectively.&#x0D; Results: Particle size, entrapment efficiency and drug deposition in Wistar Rat Skin was found to be statistically significant for nanocochleates over liposomes proving superiority of cochleates. Both the carriers sustained release of silymarin for 24h. Antimicrobial efficacy of nanocochleates against E.coli and S.aureus was significant. Inhibition of hyper proliferation of HaCaT cell lines (key mechanism by which most of the antipsoriatic drugs act) demonstrated the superiority of nanocochleates over liposomes.The nanocochleates also displayed better stability compared to liposomes due to decreased entrapment efficacy and leakage of drug.&#x0D; Conclusion: Silymarin loaded Nanocochleates could prove as a promising topical drug delivery system for the treatment of chronic skin diseases like psoriasis.