Effect of Andrographis paniculata extract and Andrographolide on the pharmacokinetics of Aceclofenac and Celecoxib in rats.

Background: In India, for the treatment of cold, fever and inflammation, people consume herbal remedies containing Andrographis paniculata Nees (APE) as main ingredient, along with NSAIDs. So the purpose of this study is to investigate the effect of APE and pure andrographolide (AN) on the pharmacokinetic of with aceclofenac (ACF) and celecoxib (CXB) after oral co-administration in wistar rats. After co-administration of APE (equivalent to 20 mg/kg of AN) and AN (20 mg/kg) with ACF (5 mg/kg) and CXB (5 mg/kg) in rats, orally, drug concentrations in plasma were determined using HPLC method. Non-compartment model was used to calculate pharmacokinetic parameters like Cmax, Tmax, t1/2, MRT, Vd, CL, and AUC. Results: Co-administration of ACF and CXB with APE and pure AN altered the systemic exposure level of each compound in vivo. The Cmax, Tmax, MRT of CXB were increased whereas Vd and Cl of CXB were decreased significantly after co-administration of CXB with APE. Whereas co-administration of CXB with AN significantly decreased Vd, CL, and MRT of CXB. The concentration of ACF was increased significantly in co-administered groups with pure AN and APE. The AUC0-∞, AUMC0-∞, MRT, Vd and t1/2 of ACF were also significantly decreased in co-administered groups, hence CL of ACF was increased significantly. Conclusion: This study concludes that APE and pure AN have effect on pharmacokinetic of CXB and ACF in rat. Not only patients but medical practitioners using Andrographis paniculata should have awareness regarding probable herb-drug interactions with ACF and CXB.

Plant Bioactives in the Treatment of Inflammation of Skeletal Muscles: A Molecular Perspective.

Skeletal muscle mass responds rapidly to growth stimuli, precipitating hypertrophies (increased protein synthesis) and hyperplasia (activation of the myogenic program). For ages, muscle degeneration has been attributed to changes in the intracellular myofiber pathways. These pathways are tightly regulated by hormones and lymphokines that ultimately pave the way to decreased anabolism and accelerated protein breakdown. Despite the lacunae in our understanding of specific pathways, growing bodies of evidence suggest that the changes in the myogenic/regenerative program are the major contributing factor in the development and progression of muscle wasting. In addition, inflammation plays a key role in the pathophysiology of diseases linked to the failure of skeletal muscles. Chronic inflammation with elevated levels of inflammatory mediators has been observed in a spectrum of diseases, such as inflammatory myopathies and chronic obstructive pulmonary disease (COPD). Although the pathophysiology of these diseases varies greatly, they all demonstrate sarcopenia and dysregulated skeletal muscle physiology as common symptoms. Medicinal plants harbor potential novel chemical moieties for a plenitude of illnesses, and inflammation is no exception. However, despite the vast number of potential antiinflammatory compounds found in plant extracts and isolated components, the research on medicinal plants is highly daunting. This review aims to explore the various phytoconstituents employed in the treatment of inflammatory responses in skeletal muscles, while providing an in-depth molecular insight into the latter.

PEGylated nanocarriers: A promising tool for targeted delivery to the brain.

Targeted drug delivery across the blood-brain barrier is an extremely challenging quest in the fight with fatal brain ailments, with the major hurdles being short circulation time, reticuloendothelial system (RES) uptake, and excretion of nanocarriers. PEGylation has emerged as a boon for targeted drug delivery to the brain. It is well established that PEGylation can increase the circulation time of nanocarriers by avoiding RES uptake, which is indispensable for increasing the brain's uptake of nanocarriers. PEGylation also acts as a linker for ligand molecules to achieve active targeting to the brain. Using PEGylation, novel approaches are being investigated to facilitate ligand-receptor interactions at the brain endothelium to ease the entry of therapeutic drugs into the brain. In addition, PEGylation made it simpler to assess the brain tissue for delivering diagnostic molecules and theranostic nanocarriers. The potential of PEGylated nanocarriers is being investigated vastly to boost the therapeutic effect several fold in the treatment of brain diseases. This review sheds light on the contribution of PEGylated nanocarriers, especially liposomes, polymeric nanoparticles, and dendrimers for brain-specific delivery of bioactives.

Neuroprotective effect of Indian propolis in ß-amyloid induced memory deficit: Impact on behavioral and biochemical parameters in rats.

The study aimed at the investigation of neuroprotective activity of macerated ethanolic extract of Indian propolis (MEEP) against ß-Amyloid 25-35 (Aß25-35) induced memory impairment in Alzheimer's disease. MEEP was administrated orally to Wistar rats at doses of 100, 200 and 300mg/kg. Behavioral performances were evaluated using morris water maze and radial arm maze. At the end of behavioral study, the brains were removed and antioxidant parameters and brain monoamines were estimated. Further acetylcholinesterase (AchE) inhibition and brain-derived neurotropic factor (BDNF) were evaluated. In addition hematological parameters and histopathological tests were also carried out. In behavioral models, MEEP significantly (P<0.05) reversed the cognitive impairment of ß amyloid-induced rats. The antioxidant potential was significantly increased (P<0.05) after administration of MEEP. Malondialdehyde levels were significantly (P<0.01) decreased in brain homogenate after treatment with MEEP extract as compared with diseased control group (group III). MEEP showed dose-dependent AChE inhibition and increased the levels of brain monoamines (P<0.05) as compared with group III. MEEP improved memory deficits by increasing BDNF in plasma (P<0.05). The study concludes that MEEP has anti-Alzheimer potential in rats through multiple mechanisms and further studies are ongoing for fractionation and biological screening.

Pharmacokinetic profile of phytoconstituent(s) isolated from medicinal plants-A comprehensive review.

Herbal medicine, the backbone of traditional medicine, has played an important role in human health and welfare for a long period. Traditional therapeutic approaches of regional significance are found in Africa, South and Central America, China, India, Tibet, Indonesia, and the Pacific Islands. The considerable scientific significance and commercial potential of traditional medicines have resulted in increased international attention and global market demands for herbal medicines, especially Chinese herbal medicines. Herbal medicines currently are the primary form of health care for the poor in the developing countries, and also are widely used as a supplement or substitute for conventional drugs in developed countries. These traditional medicines have a pivotal role in the treatment of various ailments and more than 50% of drugs used in Western pharmacopoeia are isolated from herbs or derived from modifications of chemicals found in plants. Herbal medicines usually contain a complex mixture of various bioactive molecules, which make its standardization complicated, and there is little information about all compounds responsible for pharmacological activity. Several research papers have been published that claim pharmacological activity of herbal medicines but few are discussing the role of the exact phytoconstituent. Understanding the pharmacokinetic profile of such phytoconstituents is essential. Although there are research papers that deal with pharmacokinetic properties of phytoconstituents, there are a number of phytoconstituents yet to be explored for their kinetic properties. This article reviews the pharmacokinetic profile of 50 different therapeutically effective traditional medicinal plants from the year 2003 onward.

Design, synthesis, pharmacological evaluation and computational studies of 1-(biphenyl-4-yl)-2-[4-(substituted phenyl)-piperazin-1-yl]ethanones as potential antipsychotics.

This article describes the design of biphenyl moiety linked with aryl piperazine and syntheses of fourteen 1-(biphenyl-4-yl)-2-[4-(substituted phenyl)-piperazin-1-yl]ethanone derivatives along with their pharmacological evaluation for antipsychotic activity and computational studies including quantitative structure activity relationship (QSAR) and descriptor based similarity study. All compounds were found to exhibit considerable anti-dopaminergic and anti-serotonergic activity in behavioural models. Among all derivatives, compound 1-(biphenyl-4-yl)-2-[4-(2-methoxyphenyl)-piperazin-1-yl]ethanone (3c) and 1-(biphenyl-4-yl)-2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]ethanone (3k) showed impressive antipsychotic profile with lower potency for catalepsy induction. These results were found to be sturdily matching with docking study in designing of compounds with homology model of human dopamine D2 receptor. Also the QSAR study strongly supports the obtained results.

Exploring the influence of steric, electronic and lipophilic descriptors of 1,3-diarly propenones on their anti-inflammatory activity.

BACKGROUND AND THE PURPOSE OF THE STUDY: Various compounds from natural and synthetic origins containing the 1,3-diarylpropenone structure have been reported to produce a variety of biological activities like anti-microbial, anti-inflammatory, vascular muscle relaxant, etc. A systematic analysis of the structural features responsible for anti-inflammatory activity and a possible mode of their actions were proposed to be evaluated by synthesizing a set of compounds, screening them for anti-inflammatory activity and developing a QSAR model. METHODS: Two types of 1,3-diarylpropenone derivatives were synthesized employing the Claisen-Schmidt condensation. These compounds were then screened for their in vivo anti- inflammatory activity by the carrageenin induced rat paw edema method and also for in vitro cyclooxygenase-2 (COX-2) inhibition activity using a colorimetric kit for COX (ovine) inhibitor screening assay. These derivatives and their anti-inflammatory activity data were employed for QSAR analysis on Vlife MDS 3.5 software. The molecules were divided into training and test sets based on observed activity and QSAR models were generated for the training set and validated. The activity of the molecules of the test set was predicted according to the QSAR equation fit. Possible correlation between observed anti-inflammatory activity and in vitro cyclooxygenase-2 inhibition was also studied. RESULTS AND CONCLUSION: Insignificant difference between the observed and predicted biological activity revealed that the selected electronic, steric and lipophilic parameters have a significant correlation (r(2)=0.85) with anti-inflammatory activity of the selected class of compounds. On the basis of results it may be suggested that the 1,3-diaryl-2-propen-1-ones framework is an attractive template for structural optimization to achieve better potency of anti-inflammatory activity. Similarly, the relatively low correlation between anti-inflammatory activity and cyclooxygenase-2 inhibition indicates that other modes of actions may also be responsible for the anti-inflammatory activity of the tested compounds.

A stability-indicating high performance liquid chromatographic method for the determination of diacerein in capsules.

A stability-indicating HPLC method was developed and validated for the quantitative determination of diacerein in capsule dosage forms. An isocratic separation was achieved using a perfectsil target ODS-3, 250x4.6 mm i.d., 5 microm particle size columns with a flow rate of 1 ml/min and using a UV detector to monitor the eluate at 254 nm. The mobile phase consisted of phosphate buffer:acetonitrile (40:60, v/v) with pH 4.0 adjusted with phosphoric acid. The drug was subjected to oxidation, hydrolysis, photolysis and thermal degradation. Diacerein was found to degrade in acidic, basic, and oxidative stress and also under neutral condition. Complete separation of degraded products was achieved from the parent compound. All degradation products in an overall analytical run time of approximately 10 min with the parent compound diacerein eluting at approximately 4.9 min. The method was linear over the concentration range of 1-10 microg/ml (r(2) = 0.9996) with a limit of detection and quantitation of 0.01 and 0.05 microg/ml respectively. The method has the requisite accuracy, selectivity, sensitivity, precision and robustness to assay diacerein in capsules. Degradation products resulting from the stress studies did not interfere with the detection of diacerein and the assay is thus stability-indicating.

Simultaneous determination of cinnamaldehyde, eugenol and piperine by HPTLC densitometric method.

An HPTLC densitometric method for the simultaneous determination of cinnamaldehyde and eugenol as well as trace amounts of piperine in pepper-contaminated cinnamon was developed. The applicability of the method was tested with cinnamon bark powder adulterated with pepper powder, cinnamon oil, clove powder, clove oil and a commercial preparation containing cinnamaldehyde and eugenol. The method was validated for specificity, precision, accuracy and robustness. The method was found to be precise for different concentrations of cinnamaldehyde, eugenol and piperine. The accuracy of the method was checked by conducting a recovery study at three different levels. The linearity was found to be in the ranges 52.54-735.56, 533.2-8531.2 and 50-300 ng/spot, respectively, with correlation coefficients of 0.9985 +/- 0.04, 0.9982 +/- 0.06 and 0.9937 +/- 0.11 for cinnamaldehyde, eugenol and piperine.

Effect of system variables involved in packed column supercritical fluid chromatography of stavudine taken as model analyte using response surface methodology along with study of thermodynamic parameters.

A multifactor optimization technique is successfully applied to study the effect of simultaneously varying the system variables on feasibility of stavudine analysis by packed column supercritical fluid chromatography (PC-SFC). The effect of simultaneously varying the pressure, temperature and modifier concentration was studied to optimize the method in order to obtain excellent chromatographic figures of merit. The method is based on isocratic elution using methanol-modified supercritical carbon dioxide as the mobile phase at the flow rate of 3.0 ml/min through a JASCO Finepak SIL-5, ODS [C(18) (5 microm, 25 cm x 4.6 mm, i.d.)] column support using photodiode array detection. The optimal conditions were determined with the aid of the response surface methodology using 3(3) factorial designs. From the response surface graphs optimum regions were selected to be +1, -1, and +1 for temperature (60 degrees C), pressure (20 MPa) and percent modifier concentration (17.81%, v/v), respectively. Linearity dynamic range was found to be in the range of 2.0-150.0 microg/ml with significantly high value of correlation coefficient. The method was validated for precision, robustness and recovery to assess the viability of the established method. The chromatographic limit of detection and quantitation were 0.80 and 1.50 microg/ml respectively. The method has been successfully used to analyze commercial dosage form to assess the chromatographic performance of SFC system which was found to be 99.91%+/-1.62. The present work briefs the thermodynamic applications of PC-SFC with an emphasis on the results of stavudine. The foremost of such applications is the determination of solute diffusion coefficient in supercritical mobile phase by Taylor-Aris peak broadening technique.

RAPD Analysis for Determination of Components in Herbal Medicine.

In this study, the RAPD (Random Amplified Polymorphic DNA) technique was employed for determination of the components in an Ayurvedic herbal prescription, Rasayana Churna. One-hundred-and-twenty decamer oligonucleotide primers were screened in the RAPD analysis to identify three Ayurvedic medicines, dried stem of Tinospora cordifolia, dried fruit of Emblica officinalis and dried fruit of Tribulus terestris, the Ayurvedic prescription. Primer OPC-6 simultaneously generated three distinct amplicons, each specific to one component. The marker with 600 bp is specific to Tinospora cordifolia; the marker 500 bp is specific to Emblica officinalis and the remaining marker >1000 bp was present in Tribulus terestris. Presence of three herbal medicines was determined when RAPD reaction with OPC-6 was performed. The technique was proved to contribute to the identification of components in Ayurvedic herbal preparation and thus helping to serve as a complementary tool for quality control.

Preparation and evaluation of floating risedronate sodium-Gelucire 43/01 formulations.

Single and multi-unit floating matrices of risedronate sodium were prepared using Gelucire 43/01 by melt solidification and melt granulation technique, respectively. The controlled release floating matrices were evaluated for in vitro and in vivo floating ability and in vitro drug release. Effect of aging on Gelucire 43/01 was evaluated by hot stage microscopy (HSM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), in vitro floating ability, and in vitro drug release. Multi-unit system obtained has shown initial burst release, which was suppressed in single unit system. Both single- as well as multi-unit systems showed increase in rate of drug release on aging due to changes in the properties of the Gelucire 43/01. Multi-unit matrices obtained by melt granulation were relatively easier for scale up and advantageous if the initial burst release does not cause any significant clinical adversity.

Physico-chemical characterization and stability study of glassy simvastatin.

The objective of the present study was to investigate the glass forming capability of a model drug simvastatin. The glassy material produced by melt quench technique was subjected to physico-chemical characterization and subsequent stability and enthalpy relaxation study. The chemical stability of drug during preparation of glass was tested by High Performance Liquid Chromatography (HPLC) and Infrared (IR) spectroscopy. The presence of amorphous form was confirmed by DSC and XRPD. Surprisingly, glassy simvastatin was almost stable throughout the period of stability, inspite of its Tg being relatively low. The stability and very low enthalpy recovery of glassy simvastatin perhaps could be attributed to strong inter-molecular hydrogen bonding.

Stabilization and improved in vivo performance of amorphous etoricoxib using Gelucire 50/13.

PURPOSE: Amorphous drugs have gained importance because of their advantageous biopharmaceutical properties; however, their stabilization remains a challenge. The purpose of this work was to stabilize the amorphous form of etoricoxib (ET) by using a low excipient/drug ratio to improve drug dissolution and thus bioavailability. METHODS: The effect of Gelucire and polyvinylpyrrolidone (PVP) on stabilization and bioavailability of amorphous etoricoxib (AET) was studied. X-ray powder diffractometry, differential scanning calorimetry, and scanning electron microscopy were used to study the physical state of the drug. Dissolution studies were performed for melt granules of AET with Gelucire 50/13 (MG-AET) and solid dispersion with PVP (SDP) to differentiate dissolution performance. A stability study on samples was conducted for 3 months to evaluate the physical state of the drug and its dissolution in the formulation. The in vivo performance of the optimized and stable formulation of ET was evaluated in rat. RESULTS: Dissolution of MG-AET was significantly improved as compared to AET and SDP. Both factors, amorphization of drug and melt granulation with lipid, seemed to be important for improving dissolution. Stability data revealed that MG-AET was significantly advantageous for AET stabilization, whereas PVP was not. The amount of Gelucire required for the stabilization of one part of AET was 0.5 part (by weight), whereas even 1.5 part (by weight) of PVP failed to elicit the same result. The superior in vivo performance of MG-AET has been attributed to the altered physiochemical properties of AET and the presence of lipid in the system. CONCLUSION: Gelucire can stabilize AET and improve its biopharmaceutical performance at a low excipient/drug ratio and may provide a better alternative to conventional stabilizers such as PVP.

Effect of system variables involved in packed column SFC of nevirapine as model analyte using response surface methodology: application to retention thermodynamics, solute transfer kinetic study and binary diffusion coefficient determination.

A multifactor optimization technique is successfully applied to study the effect of simultaneously varying the system variables on feasibility of nevirapine analysis by packed column supercritical fluid chromatography (PC-SFC). The optimal conditions were determined with the aid of the response surface methodology using 3(3) factorial designs. The method is based on methanol-modified carbon dioxide as the mobile phase at flow rate of 3.0 ml/min with elution through a JASCO Finepak SIL-5, [C18 (5-micron, 25 cm x 4.6 mm, i.d.)] column using photodiode array detection. The method has been successfully used to analyze commercial solid dosage form to assess the chromatographic performance of SFC system. The present work briefs the thermodynamic applications of PC-SFC with an emphasis on the results of nevirapine. The foremost of such applications is the determination of solute diffusion coefficient in supercritical mobile phase by Taylor-Aris peak broadening technique.

Spray-dried amorphous solid dispersions of simvastatin, a low tg drug: in vitro and in vivo evaluations.

PURPOSE: To obtain free flowing, stable, amorphous solid dispersions (SDs) of simvastatin (SIM), a drug with relatively lower glass transition temperature (T(g)) by spray drying technique, and to perform comparative in vivo study in rats, which could justify the improvement in rate and extent of in vitro drug release. METHODS: Dichloromethane suspensions of SIM either alone or in combination with PVP (1:1 or 1:2 parts by weight) were spray dried with proposed quantity of Aerosil 200 (1:1, 1:1:1, 1:2:2 parts by weight of SIM, Aerosil 200 and PVP, respectively). SDs were characterized initially in comparison with pure drug and corresponding physical mixtures in same ratios by drug content, saturation solubility, SEM, DSC, XRPD, IR, and in vitro drug release. SD 1:2:2 was further subjected to accelerated stability testing and checked for in vitro drug release and presence of crystallinity using DSC and XRPD. In addition, improvement in rate and extent of in vitro drug release from SD 1:2:2 was justified by in vivo study in rats. RESULTS: Combination of SD and surface adsorption techniques has been attempted to overcome the limitations of spray drying technique for amorphization of low T(g) drugs. Based on powder characteristics, drug content, saturation solubility, and feasibility of processing into tablets; SD 1:2:2 was selected as the optimized formulation. During initial characterization, SEM, DSC, and XRPD analyses confirmed the presence of amorphous form in SD 1:2:2. IR spectroscopy revealed possibility of hydrogen bonding interaction between SIM and PVP in SDs. Also, there was dramatical improvement in rate and extent of in vitro drug release of SD 1:2:2. Insignificant decrease in dissolution was observed with no evidence of crystallinity during accelerated stability studies of SD 1:2:2. Moreover in vivo study in rats also justified the improvement in therapeutic efficacy of SD 1:2:2 over pure SIM. CONCLUSIONS: Thus, present study demonstrates high potential of spray drying technique for obtaining stable amorphous SDs of low T(g) drugs.

Silk sericin as a moisturizer: an in vivo study.

BACKGROUND: Excessive transepidermal water loss (TEWL) is the one of the causes of dry skin, and skin moisturizers have been used to overcome it. AIM: The purpose of this research was to study the moisturizing effect of sericin, a silk protein. Because silk sericin has resemblance with the natural moisturizing factor (NMF), it has been studied for its application in skin cosmetics. METHODS: Sericin gels were prepared using sericin solution and with pluronic and carbopol as stabilizers. The gels were applied on the skin of healthy human volunteers and its moisturizing efficiency was evaluated by measuring the skin hydroxyproline content, impedance, TEWL, and scanning electron microscopy (SEM) results. RESULTS: Decrease in skin impedance, increase in hydroxyproline level, and hydration of epidermal cells revealed the moisturizing effect of sericin, whereas decrease in the value of TEWL may be attributed to occlusive effect, which prevents water loss from the upper layer of the skin. Skin surface topography revealed the smoothness of the upper layer of the skin as a result of moisturization. CONCLUSION: Increase in the intrinsic moisturization of skin by sericin may be attributed to restoration of the amino acids and its occlusive effect. Thus, it would become a promising and important moisturizing ingredient in moisturizing formulations.

Stability study of amorphous valdecoxib.

Formulation of poorly water-soluble drugs in the most stable dosage form for oral delivery perhaps presents the greatest challenge to pharmaceutical industry. Physical transformation of drug substance into its more soluble but metastable amorphous form is one of the approaches for improving dissolution rate of such drugs. The present study utilizes technique of spray drying for preparation of solid dispersions (SDs) and includes stability study of the same. Valdecoxib (VLD), a prototype of poorly water-soluble drugs, has been the drug of choice. The hydrophilic carriers selected were polyvinylpyrrolidone K30 (PVP) and hydroxypropylcellulose (HPC). SDs and pure VLD in the form of spray dried powder (SDVLD) in comparison with pure drug and corresponding physical mixtures (PMs) were initially characterized and then subjected to stability testing at ambient temperature and relative humidity up to 3 months. During initial characterization, increase in saturation solubility and dissolution rate was observed in all samples. DSC and XRPD studies of SDVLD and SDs suggested generation of amorphous form of drug. IR spectroscopy revealed presence of hydrogen bonding in SDs. During stability testing, there was gradual decrease in saturation solubility and dissolution rate of SDs, over the period of 3 months. While, saturation solubility of SDVLD dropped drastically within 15 days and was almost comparable with pure VLD. SD PVP retained the amorphous form of drug throughout stability period, whereas SD HPC and SDVLD presented incidence of crystallinity after 1 month and 15 days, respectively. This was justified by enthalpy relaxation studies in which, amorphous VLD showed considerable relaxation of enthalpy at Tg, while it was totally suppressed in SD PVP and partly in SD HPC. The study thus definitely reveals tremendous potential of solid dispersions of valdecoxib with PVP, from stability point of view.

The ICH guidance in practice: stress degradation studies on indinavir sulphate and development of a validated specific stability-indicating HPTLC assay method.

A sensitive, selective, precise and stability-indicating high-performance thin layer chromatography (HPTLC) method for analysis of indinavir sulphate both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of carbon tetrachloride/chloroform/methanol/10% v/v ammonia (4:4.5:1.5:0.05, v/v/v/v). Densitometric analysis of indinavir sulphate was carried out in the absorbance mode at 260 nm. This system was found to give compact spots for indinavir sulphate (Rf value of 0.43 +/- 0.02, for six replicates). Indinavir sulphate was subjected to acid and alkali hydrolysis, oxidation, dry and wet heat treatment, and photo degradation. The drug undergoes degradation under acidic and basic conditions, oxidation, dry and wet heat treatment, and photo degradation. Also the degraded products were well resolved from the pure drug with significantly different Rf values. The method was validated for linearity, precision, robustness, limit of detection (LOD), limit of quantitation (LOQ), specificity and accuracy. Linearity was found to be in the range of 100-6000 ng/spot with significantly high value of correlation coefficient r2 = 0.997 +/- 0.64. The linear regression analysis data for the calibration plots showed good linear relationship with r2 = 0.999 +/- 0.002 in the working concentration range of 1000-6000 ng/spot. The LOD and LOQ were 40 and 120 ng/spot, respectively. Statistical analysis proves that the method is repeatable and specific for the estimation of the said drug. As the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one. Moreover, the proposed HPTLC method was utilized to investigate the kinetics of acid degradation process. Arrhenius plot was constructed and activation energy was calculated.