Kollidon® SR and Sustained release

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KOLLIDON SR AND EUDRAGIT S100 EMPLOYING FOR DICLOFENAC SODIUM SUSTAINED RELEASE TABLETS IN COLON SPECIFIC DELIVERY

KOLLIDON SR AND EUDRAGIT S100 EMPLOYING FOR DICLOFENAC SODIUM SUSTAINED RELEASE TABLETS IN COLON SPECIFIC DELIVERY

By this technique, release and absorption of the drug in the upper portion of the GI tract can be minimized until the drug reaches the proximal colon. Precise colon drug delivery requires that the triggering mechanism in the delivery system only respond to the physiological condition particular to the colon. Hence, continuous effort has been made on designing colon- specific delivery system with improved site specificity and versatile drug release kinetics to accomplish different therapeutic needs. [2] The formulation should be such that when taken orally minimum amount of drug should be release up to 5 hours and the complete release up to 12 hours. Oral delivery of the drug to the colon is very valuable in the treatment of the colon diseases like ulcerative colitis, carcinomas, amoebiasis, inflammatory bowel disease (IBD) and rheumatoid arthritis and can be effectively treated by the local delivery of drugs to the large intestine whereby high local concentration of the drug can be achieved while minimizing the side effects that occurs due to the release of drug in upper GIT (Gastro Intestinal Tract) or systemic absorption.
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FORMULATION AND EVALUATION OF DEXIBUPROFEN MATRIX TABLETS FOR ORAL CONTROLLED DRUG DELIVERY

FORMULATION AND EVALUATION OF DEXIBUPROFEN MATRIX TABLETS FOR ORAL CONTROLLED DRUG DELIVERY

In the present research work, the compressed tablet properties such as percentage of drug content, hardness, average weight and weight variation obtained an acceptable range and the values meet pharmacopeias limits. The swelling behaviors of formulated tablets remarkably increase with optimum proportion of polymer and diluent level. The optimum proportion of HPMC K15M and Pharmatose 200M (DX-4) shows the gradual swelling behavior and gives a great contribution to sustain the drug release for extended period of time. The formulation containing higher concentration kollidon SR as hydrophobic retardant and lower level of Pharmatose 200M (DX-10) shows low swelling behavior which effects on irrelevant drug release from the matrix tablets corresponding to specified time period. The in-vitro drug release significantly decreases with variable concentration of polymer and diluent ratio. The formulated drug loaded matrix tablets in SGF pH 1.2 show less than 20% w/w of drug release due to hydrophobicity of drugs, but maximum amount of drug release (>60 %w/w) in pH 7.4 at 6 h followed by sustaining up to 12 h. The kinetic drug release mechanism of optimized dexibuprofen matrix tablets of batch DX-4 was found to be linear and close correlation with huguchi matrix diffusion followed to Korsmeyer and Peppa‟s model and good regression co- efficient was observed due to diffusion and erosion mechanism of polymeric chains and shown the diffusion co-efficient (n) values in the range of 0.8548 to 1.1356. This indicates, the drug release from matrix tablets by both diffusion and erosion mechanisms followed by super case-II transport. Based on the investigated results, it was concluded that the polymer and diluent ratio modify the release of drug in different environmental pH conditions, capable of exhibiting to sustained release properties, environmentally stable and feasible for further scale up industrial production.
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Design and in vitro evaluation of compressed Kollidon® SR based Salbutamol
Sulphate microcapsules: Effect of talc

Design and in vitro evaluation of compressed Kollidon® SR based Salbutamol Sulphate microcapsules: Effect of talc

bronchodilator in the treatment of reversible bronchospasm. It is absorbed rapidly when administered orally. The plasma half-life of salbutamol was calculated to be 2-7 hrs. [5]. Its usual dose is 2-4 mg, 3-4 times daily [6]. In the present study water insoluble polyvinyl acetate and polyvinyl pyrrolidone (Povidone) based matrix polymer (Kollidon ® SR) and talc were used for preparing microcapsules where kollidon ® SR was used as rate controlling model polymer. This water insoluble polymer (povidone part is water soluble but polyvinyl acetate part is water insoluble) can be used in different types of sustained release dosage forms like tablets, pellets and granules [7]. But its excellent flow ability and compressibility makes it suitable for sustained release matrix tablet by direct compression [7-10]. The drug content in microcapsules is conventionally determined by extracting the drug or dissolving the dosage form in a solvent followed by quantification of the drug using an appropriate analytical technique [11-13]. In this paper the effect of variable concentrations of talc on release of salbutamol sulphate from kollidon ® SR based compressed microcapsules have been discussed.
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Journal of Applied Pharmaceutical Science

Journal of Applied Pharmaceutical Science

The objective of this study was to develop a sustained release matrix tablet Metoprolol Succinate by cost saving and production efficient process. Among various tablet manufacturing process, direct compression is the simplest and cost saving process. Different trials were formulated and evaluated using different concentrations of directly compressible grade Kollidon SR as release retardant. The formulated tablets were evaluated for physical and dissolution study using buffer medium. The most outstanding aspect of this study is to monitor the influence of different percentage of Kollidon SR on release rate from the matrix tablet. In this study, influence of different ratio of polymer concentration on drug release was evaluated. The release pattern of different batches were evaluated for Zero order, Higuchi, First order, Krosmeyer-Peppas and Hixson-Crowell kinetics and showed that all the batches followed best the Higuchi kinetics. The drug release kinetics was found to be governed by the amount of the polymer in the matrix system. The higher polymeric content in the matrix decrease the release rate of the drug. The nature of the drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation and therefore followed non-Fickian or anomales release. The studies indicated that the drug release can be modulated by varying the concentration of the polymer. Among the four formulations, formulation 1 is the best formulation as it controls the release best and best linearity for zero order plots.
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Formulation Design and Characterization of Kollidon SR Based Trimetazidine Dihydrochloride Matrix Tablets

Formulation Design and Characterization of Kollidon SR Based Trimetazidine Dihydrochloride Matrix Tablets

high linearity, with correlation coefficient (r ) value of 0.93 or more. The 'n' value lies between 0.45<n<0.89 (Korsmeyer-Peppas model) demonstrating that the mechanism controlling the drug release was the anomalous non-Fickian or anomalous release. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with formulation 1. Therefore, the results generated in this study showed that the formulated sustained release matrix tablets deliver the drug through a combination of both diffusion and erosion controlled mechanism.
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Characterization of Eudragit types and Kollidon SR inter-polymer complexes and their effects on the drug release

Characterization of Eudragit types and Kollidon SR inter-polymer complexes and their effects on the drug release

Poly-methacrylate copolymer (Eudragit; Eud) is a unique polymer and produces different characteristics depending on the substitution as a pH dependent polymer (Patra et al., 2017). Usually, it uses to modify the drug release for delayed release formulation (Eud L), protecting from an ambient condition or taste masking (Eud E), or as a material for sustained release formulation (Eud RS/ Eud RL) (Elzayat et al., 2017; Thakral et al., 2013). Blending of Eud RS and KSR in the film coating of HPMC matrix tablet enhanced the mechanical robustness of HPMC. This polymer can interact with other polymers in blending, especially in unconventional blending of Eudragit RS with KSR (Ali et al., 2017). Theoretically, several mechanisms in the interaction between polymers can be involved, i.e., hydrogen bonding with Eud L, Van der Waals interaction with Eud E or Eud RS. Meanwhile, the IPC based on ionic interaction/inter-polyelectrolyte, i.e., Eud E-Eud L basically can alter the physicochemical and physicomechanical properties (Khutoryanskiy, 2007; Robertis et al., 2015). The physicochemical and physicomechanical characteristics of IPC depended on the native characteristic and its interaction. Hence, the purpose of this study was to characterize the IPC of several Eud types, such as Eud RS, Eud L, and Eud E, with KSR and elucidate their effects on the drug release. In this study, Theophylline, THP, was selected as a drug model. THP has solubility in water of 8.3 mg/ml, and according to the functional group, it includes in weak acid drug which has pKa value of 8.6. Due to this characteristic, it has a negligible effect on solubility in range pH of 1.2–6.8. Therefore, for intended use, this drug has no pH effect on drug release during pH shifting (Zhang et al., 2017). As pharmacological perspective, THP is applied for asthma treatment and it has a narrow therapeutic window which controlled release formulation is suitable to address
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“Development of Different Polymer Matrix Systems for Galantamine Hydrobromide Sustained Release” by Angel Aleksiev, B. Kostova, D. Rachev, Bulgaria.

“Development of Different Polymer Matrix Systems for Galantamine Hydrobromide Sustained Release” by Angel Aleksiev, B. Kostova, D. Rachev, Bulgaria.

This paper outlines the development of controlled release matrix systems containing galantamine hydrobromide. The model compositions were developed by the direct compression technique, using a variety of hydrophilic and hydrophobic polymer carriers: Methocel® K100LV, Methocel® K4M, Kollidon® VA64 and Kollidon® SR at different concentrations. The swelling and erosion rate, as well as in vitro drugrelease characteristics of the studied matrices were investigated. Various mathematical models were used in order to evaluate the in vitro release kinetics and mechanism of galantamine hydrobromide. It was found out that the increase of the polymer quantity leads to change in the drug release mechanism from Fickian diffusion to Anomalous (non-Fickian) diffusion. Keywords: galantamine hydrobromide, drug delivery systems, sustained drug release, matrix tablets.
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A brief review on Kollidon

A brief review on Kollidon

Kollidon grades among the synthetic excipient it is said to be one of the essential substances in the pharmaceuticals and cosmetic industries. The soluble kollidon grades were synthesized by w. reppe in 1939; a number of the product followed by including insoluble grades, copolymeristates and sustain release preparation for numerous applications. The insoluble grades (crospovidone) are prepared using a physical cross-linking process as popcorn polymers of vinyl pyrrolidone. kollidon VA 64 (Copovidone) is a water-soluble copolymeristate of vinylpyrrolidone, and vinyl acetate is mainly used as a binder in tablet, granules, capsules, and coating process. For sustained release purpose, a mixture of polyvinyl acetate and povidone in a ratio of 8:2 is available under the name of kollidon SR which mainly used as controlled release system. Kollidon soluble grade has a wide range of applications in the oral formulation include enhancement in solubility and bioavailability of the drug, immediate release, taste masking, increase binding capacity, stability, improve the activity of pore formation. The examples of soluble grade of kollidon (Povidone) are kollidon 12 PF, 17 PF, 25, 30, 90F, kollidon VA64 (Copovidone), insoluble grade (Crospovidone) are kollidon CL, CL-F, CL-SF, CL-M and kollidon SR grade which is mixture of polyvinyl acetate and povidone in ratio of 8:2 for sustain
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PREPARATION AND IN VITRO EVALUATION OF ETODOLAC EXTENDED RELEASE TABLETS PREPARED BY WET GRANULATION METHOD EMPLOYING KOLLIDON® SRArun Kumar Arumugarajan*,G. Geetha, Bhabani Shankar Nayak DOWNLOAD/VIEW

PREPARATION AND IN VITRO EVALUATION OF ETODOLAC EXTENDED RELEASE TABLETS PREPARED BY WET GRANULATION METHOD EMPLOYING KOLLIDON® SRArun Kumar Arumugarajan*,G. Geetha, Bhabani Shankar Nayak DOWNLOAD/VIEW

Etodolac, 2-(1,8-diethyl-4,9-dihydro-3H-pyrano[3,4- b]indole-1-il)acetic acid is an example of non- steroidal anti-inflammatory drugs (NSAIDs) [4]. It is especially beneficial in treatment of chronic conditions of arthritis, osteoarthritis and similar rheumatismal diseases [5]. Etodolac is a medicine with a short elimination half life of 8 h and low and pH-dependent solubility between pH 3 to 7 [6]. Thus in order to maintain the effective plasma levels of the drug, its frequent administration are needed which would in turn lead to NSAID-related side effects on gastro-intestinal (GI) system [7]. Also once-a-day sustained action medications for drug molecules with short half lives typically like Etodolac present formulation problems because of their relatively short residence time into GI tract before elimination [8,9]. Thus the present study aimed to develop an extended release tablet dosage form of Etodolac by wet granulation method employing semi-synthetic polymer that is Kollidon® SR.
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PREPARATION AND EVALUATION OF SUSTAINED RELEASE (SR) MATRIX TABLETS OF AZITHROMYCIN USING DIFFERENT POLYMERS

PREPARATION AND EVALUATION OF SUSTAINED RELEASE (SR) MATRIX TABLETS OF AZITHROMYCIN USING DIFFERENT POLYMERS

The most commonly used method of modulating the drug release is to include it in a matrix system [1]. An effort was therefore made to develop simple and effective sustained-release Azithromycin tablets using a polymer matrix system. Hence, in the present study, an attempt has been made to develop the sustained-release matrix tablets of Azithromycin using hydrophilic polymer HPMC K4M, Gaur gum and carrageenan gumthe sustained pattern of it was evaluated by in-vitro drug release for 12 hours. The drug release data were plotted using various kinetic equations (zero-order, first-order, Higuchi’s kinetics, Korsmeyer’s equation, and Hixson-Crowell cube root law) to evaluate the drug release mechanism and kinetics [2].
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Clarithromycin based oral sustained release nanoparticulate drug delivery system

Clarithromycin based oral sustained release nanoparticulate drug delivery system

The gliadin defines a group of polymorphic proteins extracted from gluten, which are soluble in ethanolic solution and show a remarkably low solubility in water except at extreme pH. Due to these physicochemical properties, gliadin nanoparticles can be prepared by desolvation method for macromolecules, using environmentally acceptable solvent such as ethanol and water. These macromolecules showed a high capacity for loading drug and were soluble without further chemical or physical cross linking treatment. In the present system, the diffusion of ethanol (good solvent for gliadin), from the gliadin solution in to the aqueous medium, drastically reduced the solubility of gliadin solution, forming nanoparticles in the solution. Gliadin nanoparticles have shown the average particles size range of 250-500 nm with positive zeta potential of 22.8 mV. The gliadin nanoparticles were spherical with smooth surface. (fig. 1.) The % drug entrapment of nanoparticles indicated that at different gliadin concentration, the % drug entrapment were 23.7±2.3, 41.6±3.4, 67.1±1.3 and 63.6±2.1, respectively. The release of clarithromycin mainly depends upon the gliadin concentration. The burst release of clarithromycin from nanoparticles at initial stage resulted from the dissolution of drug crystals on the surface of nanoparticles; with increasing gliadin concentration, the release rate of clarithromycin from nanoparticles decreased drastically. The smaller nanoparticles released the drug more rapidly than larger ones in PBS and SGF at initial stage, as the smaller devices possess the larger surface area.
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Journal of Applied Pharmaceutical Science

Journal of Applied Pharmaceutical Science

The micromeritic properties such as of bulk density, tapped density, Angle of repose, compressibility index, Hausner’s ratio and particle size distribution of Ranitidine Hcl immediate release layer blend and Diclofenac Sodium sustained release layer were studied. The overall results were shown in Table No. 3 and 4. The value of bulk density indicates good packing characteristics. The compressibility index of the formulation found to be below 15 indicating excellent flow properties of granules which were further confirmed by determining the angle of repose, it is in the range of 25° to 27° which indicates good flow properties.
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Volume 2 | Issue 1 - 2012

Volume 2 | Issue 1 - 2012

Sustained release floating matrix tablets were prepared by direct compression method. All the excipients were weighed accurately and sifted through 40# mesh screen. Drug was geometrically mixed with excipients followed by addition of the matrix forming polymer and gas generating agent. Mixing was done and final sifting was carried through 22# mesh screen. Pre-lubrication and lubrication was done for 5 and 2 minutes, respectively. Compression was carried out by manual single punching machine. The formulated tablets were further evaluated of the tablet parameters. In all the formulations, polymers concentration was varied from 10 to 50% of the total weight. The composition of various formulations is shown in the Table 1.
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Transdermal donepezil on the treatment of Alzheimer&#39;s disease

Transdermal donepezil on the treatment of Alzheimer&#39;s disease

Abstract: Alzheimer’s disease (AD) is the most common type of senile dementia, characterized by cognitive deficits related to degeneration of cholinergic neurons. The first anti-Alzheimer drugs approved by the Food and Drug Administration were the cholinesterase inhibitors (ChEIs), which are capable of improving cholinergic neurotransmission by inhibiting acetylcholinesterase. The most common ChEIs used to treat cognitive symptoms in mild to moderate AD are rivastigmine, galantamine, and donepezil. In particular, the lattermost drug has been widely used to treat AD patients worldwide because it is significantly less hepatotoxic and better tolerated than its predecessor, tetrahydroaminoacridine. It also demonstrates high selectivity towards acetylcholinesterase inhibition and has a long duration of action. The formulations available for donepezil are immediate release (5 or 10 mg), sustained release (23 mg), and orally disintegrating (5 or 10 mg) tablets, all of which are intended for oral-route administration. Since the oral donepezil therapy is associated with adverse events in the gastrointestinal system and in plasma fluctuations, an alternative route of administration, such as the transdermal one, has been recently attempted. The goal of this paper is to provide a critical overview of AD therapy with donepezil, focusing particularly on the advantages of the transdermal over the oral route of administration.
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DEVELOPMENT AND IN VITRO EVALUATION OF MICRONIZED SUSTAINED RELEASE MATRIX TABLET OF CARVEDILOL

DEVELOPMENT AND IN VITRO EVALUATION OF MICRONIZED SUSTAINED RELEASE MATRIX TABLET OF CARVEDILOL

It also has multiple spectrums of activities such as antioxidant property, inhibition of smooth muscle proliferation and calcium antagonistic blocking activity 10, 11, 12 . Carvedilol is widely used as immediate-release (IR) tablet formulation to treat essential hypertension and mild to severe congestive heart failure 13 . Carvedilol free base is practically insoluble in water and thus poorly absorbed from gastro intestinal tract. It exhibits poor absolute bioavailability of 25-35% 14 . Half life of carvedilol is 6-8 hrs 15 . Recently a phosphate salt of carvedilol is developed with improved aqueous solubility and chemical stability by protonation of the secondary amine as a salt 16 . A new controlled release capsule of carvedilol phosphate was recently marketed with dose strength of 10, 20, 40 and 80 mg free base of carvedilol administered once daily 13 . The goal to design controlled release drug delivery systems (CRDDS) was to deliver drug at
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FORMULATION AND IN VITRO EVALUATION OF DAPAGLIFLOZIN AND SAXAGLIPTIN BILAYERED TABLETS

FORMULATION AND IN VITRO EVALUATION OF DAPAGLIFLOZIN AND SAXAGLIPTIN BILAYERED TABLETS

Dapagliflozin (DG) is a sodium glucose cotransporter-2 (SGLT-2) inhibitor and Saxagliptin (SG) is a dipeptidyl peptidase-4 (DPP-4) inhibitor. The aim of the present work is to formulate a bilayered tablet (BT) of DG as immediate release (IR) layer and SG as sustained release (SR) layer by direct compression method for the effective treatment of type 2 diabetes mellitus. Type and concentration of superdisintegrant among [sodium starch glycolate (SSG)/Lycoat RS720/ Ludiflash] was optimized to enhance the dissolution rate (DR) of DG from the IR layer of BT. Type and concentration of SR polymer among (Carbapol 940/ Karaya gum/ HPMC K15M) was optimized to extend the release of SG up to 12 h with zero order release profile from the SR layer of BT. It was concluded that the optimization of the ratio of SG: SR polymer (HPMC K15M), had significant effect on extending the release profiles of SG. The ratio of SG: HPMC K15M at 1:18 respectively forms a better matrix for the extending the release of SG up to 12 h from the SR layer of BT. The optimized formulation; BT9 [IR9 (6% w/w Ludiflash as superdisintegrant and SR9 (with 60% HPMC K15M as SR polymer)] releases 100% of DG from the IR layer with in 45 min and extends the release of SG up to 12 h with a better zero order release profile (r 2 =0.994). It passes the accelerated stability studies as per
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Formulation Development and Evaluation of SR Matrix Tablets of Stavudine

Formulation Development and Evaluation of SR Matrix Tablets of Stavudine

The objective of the present research was to study the effect of two different types of polymer such as HPMCK4M and Eudragit RS 100 in formulation of a sustained release (SR) matrix tablet of stavudine. Stavudine and polymer compatibility studies were performed using Fourier transform infrared spectroscopy (FT-IR) and Differential scanning calorimetry (DSC). The pre-compression mixture formulation was evaluated for flowability and compressibility. The tablets were prepared by direct compression method. The effect of concentration and type of polymer on In-vitro drug release and release kinetics was studied extensively. The optimized formulation was subjected to stability testing. FT-IR and DSC studies revealed no interaction between stavudine and polymers. Flowability and compressibility study of pre-compression powder formulation showed that these formulations were within the theoretical range for processing into tablet dosage form. In-vitro release studies exhibited that the drug release was sustained up to 12 h for SR matrix tablets prepared with HPMCK4M whereas EudragitRS100 based SR matrix tablets could not sustain the release for more than 6 h. Incorporation of PVPK90 as a dry binder assisted in maintaining matrix integrity of Eudragit RS100 based SR matrix tablet and sustained the release up to 12 h. Stability studies showed no significant change in drug content for both strip packed and unpacked tablets. Hence both type of polymers mentioned above can be used for the preparation of SR matrix tablets of stavudine.
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FORMULATION AND IN VITRO EVALUATION OF GASTRORETENTIVE BILAYER FLOATING TABLETS OF LOSARTAN POTASSIUM

FORMULATION AND IN VITRO EVALUATION OF GASTRORETENTIVE BILAYER FLOATING TABLETS OF LOSARTAN POTASSIUM

The aim of present study was to formulate and evaluate Gastroretentive bilayer floating tablets of Losartan potassium using direct compression technology. Bilayer floating tablets comprised two layers, i.e. immediate release and controlled release layers. The immediate release layer comprised Crospovidone as a super disintegrant and floating layer comprised Sodium carboxy methyl cellulose (SCMC), Metolose SR and Sodium alginate as the release retarding polymers. Sodium bicarbonate was used as a gas generating agent. The powder blends were evaluated for pre-compression parameters. Compressed tablets were further evaluated for hardness, friability, weight variation, dimensions, Drug Content Uniformity, In-vitro buoyancy and dissolution studies. All the formulations showed good results which were compliance with pharmacopoeial standards. In-vitro dissolution studies were performed in USP-XXIII dissolution test apparatus, type II (paddle method) in 1.2pH buffer. More than 99% Losartan potassium of was released from the immediate release layer within 30 min. The results of dissolution studies indicated that formulation BFT8 (drug to polymer[SCMC] 1:0.25), the most successful of the study, exhibited drug release of approximately 98% at 12 th hour with more than 12h buoyancy with floating lag time of 93seconds. An increase in drug release was observed on decreasing polymer ratio. The drug release mechanism of all the formulations was found to be Fickian diffusion-controlled drug release.
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FORMULATION OF IMMEDIATE RELEASE (IR) ATORVASTATIN CALCIUM PELLETS AND SUSTAINED RELEASE (SR) GLIBENCLAMIDE FOR FIXED DOSE COMBINATION DOSAGE FORM

FORMULATION OF IMMEDIATE RELEASE (IR) ATORVASTATIN CALCIUM PELLETS AND SUSTAINED RELEASE (SR) GLIBENCLAMIDE FOR FIXED DOSE COMBINATION DOSAGE FORM

Preparation of drug-loaded sustained release glibenclamide pellets A uniform dry powder mixture (batch size 100 g) containing glibenclamide, MCC ( Avicel PH 101 ), locust bean gum, and gum ghatti/ guar gum is taken in polyethylene bag in different concentrations as shown in Table 1. The above mixture was then granulated using © 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2018.v11i12.26629

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DESIGN AND CHARACTERIZATION OF DONEPEZIL HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLETS

DESIGN AND CHARACTERIZATION OF DONEPEZIL HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLETS

Release of the prepared tablets was determined using U.S.P type II paddle type dissolution rate test apparatus (TDT-06P, Electrolab) using 900 ml of 0.1 N HCl medium for 120 minutes, then in phosphate buffer pH 6.8 medium for 12hrs. as dissolution medium. The temperature of 37±1ºC was maintained and paddle was adjusted at 25 rpm throughout the experiment. Withdrawn not less than 5 ml of the dissolution solution at 1, 2, 4, 6, 8, 10, 12, 14hr time interval and were replaced with 5 ml of fresh dissolution media after each withdrawal. Filtered each sample through a membrane filter with pore size of not more than 0.45 mm. The samples were analyzed after appropriate dilution by UV spectrophotometer at λ max 229 nm.
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