VOLUME 4(6) November - December 2013

PHARMANEST JOURNAL

VOLUME 4(6) November - December 2013

PHARMANEST JOURNAL

PHARMANEST - An International journal of Advances in Pharmaceutical Sciences

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UV spectrophotometric method have been developed for the estimation of Deflazacort in pure and its pharmaceutical formulations. In UV method Deflazacort showed absorption maximum at 242.8nm in methanol medium and it obeyes Beers law in the concentration range of 5-25µg/ml.

INTRODUCTION

Sleep is a naturally recurring state

Snoring

Snoring is the loud noise which people make while they are breathing during sleep.

It shows vibrations in tissues as the person is trying to suck air in.

Narcolepsy

It is a sleep disorder that involves excessive, uncontrollable sleepiness at day time. It is mainly caused by dysfunction of the brain mechanism that controls sleep and wake process 6 . In narcolepsy, sleep attacks can happen while in the middle of talking, working or even driving. Since it is a chronic neurological disorder, symptoms may include one or more of the following:

Teeth Grinding

Is an increase in the activity of the jaw muscles while sleeping. This condition occurs in children and is equally common

Restless Legs Syndrome (RLS)

Restless Legs Syndrome is a sleep disorder that causes an almost irresistible urge to move legs.

INTRODUCTION

EVALUATION OF THE PREPARED

BUCCAL TABLETS

All the tablets were evaluated for different parameters such as hardness, weight variation and friability 5 .

Drug content

Twenty tablets were collected and powdered. The powder equivalent to 50 mg of drug was weighed accurately, dissolved in 100 ml of phosphate buffer pH 6.8. The solution was filtered, suitably diluted and an aliquot was analyzed at 224nm 6 .

Swelling studies

Three buccal tablets were weighed individually (W1) and placed separately in 2% agar gel plates and incubated at 37±1 0 c.

After every 2h time interval until 6h the tablet was removed from the petridish and excess surface water was removed carefully with blotting paper. The swollen tablet was then reweighed (W2) and the swelling index were calculated by using the formula given in equation 7

Swelling index = (W2-W1)/W1 X 100

Where, W1 = initial weight of the tablet W2 = final weight of the tablet

Surface pH study

The tablet was allowed to swell by keeping in contact with 1 ml, of distilled water for 2h at room temperature. The pH was measured by bringing the electrode in contact with the surface of the tablet and allowing it to equilibrate for 1 min 8 .

Ex-vivo mucoadhesion time

The ex vivo residence time was found using Table 3

Table 3

INTRODUCTION

Cosmetics are substances used to enhance the beauty and appearance. There is a very large role that the cosmetics play in Table1

Table 1

cosmetic Industry has witnessed a rapid growth in sales in the last couple of decades. It is growing at an average rate of almost 20% annually. The range of Indian consumer is constantly bombarded with advertisements and information on new cosmetic products which often translates into the desire to purchase them. Now-a-days, these advertisements and claims of cosmetics are major issue globally. The legislation to control these advertisements and claims are weak and not in the interest of the consumers in India 11 .As per the drugs and cosmetics act, it is made mandatory to produce any report of test or analysis for advertising any claims confusion in terms of a proper code to follow by the industry and the authority to regulate or guide the pattern of advertising.advertising practices. ASCI entertained and disposed-off complaints based on its Code of Advertising Practice (-ASCI Code‖). On certain occasions, however, the ASCI orders were set aside by the courts as ASCI being

Registration and Licensing procedure:

The application for license to manufacture Table 3.

Table 3

.Similarities and differences in regulations of cosmetics between India and USYes, but no direction is given in the D&C Act and Rules regarding the nomenclature of Colouring agents.Yes, Labeling should specify the list of ingredientsAvailable online: www.pharmanest.net Control is undertaken by FDA/FTC and other Authorities. If the manufacturer does not have data to prove the safety of this product, the compulsory warning -The safety of this product has not No post marketing reporting system Yes. Voluntary Cosmetic Registration Program and MedWatch Advertisement Drugs and magic remedies Act Regulated by Advertising Standards Council of India (ASCI) Indian Society of Advertisers (ISA) and Drug controller general of India (DCGI)

INTRODUCTION

Cancer is the most dreadful disease and is the leading cause of mortality with millions of new cases every year 1 The photothermal affect of gold nanoparticles involves the following steps.

Step 1. Cellular uptake of gold nanoparticle by endocytosis.

Step 2. Focusing the near infrared radiation, leads to conversion of light into heat and this finally leads to photo thermal effect on the cancerous cell specifically without eliciting its activity upon the normal cells.

Applications of silver nanoparticles:

Silver nanoparticles are the most commonly used in medicine, material sciences and chemistry 54 . Silver nanoparticles are used as anti-microbial agents and are used in the treatment of burns and wounds 55,56 .

Silver nanoparticles are also used as components of dental alloys 57

SYNTHESIS OF CHITIN Co (ACETATE/PROPIONATE) (CAPC) MIXED ESTERS

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RESULTS

Table .

Methods

As the name implies, this is a process where moisture is used to activate the granule formulation, but the granules are not heat dried.

The MADG Process:

The Moisture Activated Dry Granulation involves two major stages:

Blending (Lubrication):

Load magnesium stearate along with granules into octagonal blender and blend for 3min, 5 min and 7 min.

Load magnesium stearate along with granules into octagonal blender and blend for 3min.

Compression:

Compression of efavirenz tablets as per the following specifications.

Compression of efavirenz tablets are maintained same.

Observation: Dissolution is found to be normal by changing the mesh size.

Further trials are done to optimize the turret speed of the tablet compression machine.

Compression of efavirenz tablets are maintained same.

Compression is carried out at 20, 25

and 30 rpm turret speed.

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Compression of efavirenz tablets are maintained same.

Compression is carried out at 20-25 rpm turret speed. The tablets met the USP tests that were not more than 2 tablets were outside the percentage limit and no tablets differed by more than 2 times the percentage limit.

Observation:

 Increase in kneading time and

Trail-4

Sifting:

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Volume 4 |Issue 6| November-December 2013

Pre-Compression

3) Hardness:

Hardness of the tablets will be determined by breaking it between the second and third fingers with thumb being as a fulcrum. There will be a sharp snap the tablet will be deemed to have acceptable strength.

Hardness of the tablets will be determined by Stokes Monsanto

Hardness Tester and the hardness should be found within the range of 3.5-5.5 kg/cm².

4) Friability

8) Dissolution by UV spectroscopy:

Dissolution means the process by which solid substance enters in the solvent to yield a solution. It is controlled by the affinity between the solid substance and the solvent. It is a process in which a solid substance solubilizes in a given solvent that is mass transfer from the solid surface to the liquid phase.

Types of dissolution apparatus:

Different types of dissolution apparatus are used. They are: i) Apparatus 1 or rotating basket type ii) Apparatus 2 or paddle assembly type iii) Apparatus 3 or reciprocating cylinder type iv) Apparatus 4 or flow through cell type v) Apparatus 5 or paddle over disk type vi) Apparatus 6 or cylinder type vii) Apparatus 7 or reciprocating holder type.

RESULTS

Pre-Compression Characteristics

Dissolution Studies

The dissolution is found to be in the lower limit in the trail 2 since the drug release is less than 75 % in 45 minutes, to overcome that the mesh sizes are changed in the multi mill in the trail 3.Dissolution is carried out in 900 ml 2% SLS in purified water USP apparatus II, paddle with 50 rpm.The release of the drug efavirenz is more than the 75% in the trail 3, 4 and 5.Trail 5 has showed the optimum dissolution values.  Turret speed is optimised to 20 -25 rpm.

INTRODUCTION

Synthesis of 3-(benzofuran-2-yl)-5-(substituted phenyl)-4, 5dihydroisoxazoles (2a-j)

To a mixture of 1-(benzofuran-2-yl)-3- Table 4.

Table 4

The need for structurally diverse compound libraries for screening in lead discovery has driven the development of new strategies for the preparation of organic molecules in neat conditions. One of those high-speed

RESULTS AND DISCUSSION i) Chemistry:

Synthesis of 1-(benzofuran-2-yl)-3phenylprop-2-en-1-one (1a)

INTRODUCTION

CHEMICAL AND INSTRUMENTS

All chemicals used were analytical grade.

Silymarin was obtained from micro lab Bangalore and other chemicals were obtained from Rankam India pvt ltd. UV spectra were recorded in Shimadzu 1601

UV-Visible spectrophotometer.

HEPATOPROTECTIVE STUDY

Induction of Liver Damage:

The rats were divided into 7 groups of six animals each. Group I served as a control, The liver are removed and weighted for histological examination.

STATISTICAL ANALYSIS

The results were expressed as mean±SEM.

The statistical analysis was carried out using one-way analysis of variance (ANOVA) followed by Dunnett's "t" test. The values of P<0.01 and P<0.001 were considered to indicate a significant difference between the groups.

RESULTS AND DISCUSSION

Table .

MATERIALS AND METHODS

Plant Materials

The plant materials i.e. rhizomes of Costus speciosus ( Figure 1) The mark is allowed to dry such that the traces of residual solvent are evaporated.

Figure 1

Then the same is packed in the extractor and extraction is performed using the next solvent. After extraction with the last solvent i.e. methanol is completed, the mark is pressed and the crude drug was placed for aqueous maceration for 24hrs.

Phytochemical Analysis

The crude drug extracts obtained from successive extraction was subjected to extensive phytochemical screening. 4,5,6,7 The results are depicted in Table 1. Table 2. The percentage of ash with reference to the air -dried drug was calculated.The results of total ash are tabulated in Table 3. The results of acid-insoluble ash are tabulated in Table 3. Table 4. Table 4. The results of loss on drying are tabulated in Table 5. The crude extracts obtained from successive extraction of rhizomes of C.speciosus were subjected to TLC characterization with the help of different solvent systems. The results of TLC are summarized in Table 6.

Table 1

Table 2

. Fluorescence characteristics of the powdered rhizome of Costus speciosusThe objective of ashing vegetable drugs is to remove all traces of organic matter, which may otherwise interfere in an analytical determination. On incineration, crude drugs normally leave an ash usually consisting of carbonates, phosphates and silicates of sodium, potassium, calcium, and magnesium. The total ash of a crude drug reflects the care taken in its preservation. A higher limit of acid insoluble ash is imposed especially in cases where silica may be present or when the calcium oxalate content of the drug is very high. Some analysis favour mixing of sulfuric acid with the powdered crude drug before ashing and this sulphated ash is normally less fusible than ordinary ash. 8Determination of Total Ash 8A silica crucible was heated to red heat for 30 minutes and allowed to cool in a desiccator and then weighed. After that about 1 g of the powdered drug was

Table 3

Table 4

. Extractive value of rhizomes of C.speciosus

Table 5

. Loss on drying value of rhizomes of C.speciosus

Table 6

Determination of Acid -Insoluble Ash

Determination of Water -Soluble Ash

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* -Vanillin-sulphuric acid reagent (VS) # -Anis aldehyde-sulphuric acid reagent (AS)

RESULT

Microscopy

The TS of the rhizome showed cork cells distinguishable into outer and inner cork.

The outer cork is composed of ten layers of thick, dark brown colored, irregular parenchymatous cells containing numerous epidermal trichomes( figure 3 to figure5).

Figure 3

were collected from Mohonaghat area of Dibrugarh district of The rhizomes of Costus speciosus was first washed thoroughly under running water to remove traces of soil particles adhered to it. The rhizomes were then cut into small pieces and subjected to shed drying for about three to four weeks. in colour. The seeds are black with white aril. Flowering time of the plant is from August to October. 3

Powder/Florescence Analysis

Ash Value

The ash values (Total ash, acid insoluble ash, and water soluble ash) of C. speciosus are reported in table 3.

The total ash, acid insoluble ash and water soluble ash was found to be 10.07%w/w, 2.43%w/w and 6.43%w/w respectively. The result revealed the presence of considerably high amount of inorganic substances in the rhizomes of C. speciosus. A high ash value is indicative of contamination, substitution or adulteration.

Extractive Value

The extractive values of the rhizome of C.

Table . 1

Table 3 .

Table .

Therapeutic uses of Dimercaprol

 In acute poisoning due to Mercury, Gold Antimony Bismuth and Thallium.

 As an adjuvant to Penicillamine in copper poisoning and in Wilson"s disease.

 As an adjuvant to calcium sodium edetate in lead poisoning.

Deferiprone

This is an orally effective, Iron chelator, less effective than Desferrioxamine.

Uses of Deferiprone

1. In acute Iron poisoning.

2. In Iron overload during liver cirrhosis.

INTRODUCTION

Lipid-based formulations are well known approach to enhance water solubility and oral bioavailability particularly, the self-Microemulsifying drug delivery system (SEDDS) 1,2 . SEDDS formulations are isotropic mixtures of an oil, a surfactant, a co surfactant (or co solvents), and a drug.

The basic principle of this system is its ability to form fine oil-in-water ( Table 2.

Table 2

.Formulation of Drug Loaded Preparation

MICROMERITIC PROPERTIES OF S-

SEDDS 12,13

All S-SEDDS were evaluated for micromeritic properties such as angle of repose, bulk and tapped density, Carr's index and Hausner's ratio these properties are listed in Table 3.

Table 3

No significance difference in any of the physical properties was observed for all S-SEDDS powders.

DRUG CONTENT 14

The drug content of Lamotrigine in each formulation was estimated by weighing out Available online: www.pharmanest.net 2. The dissolution rate and extent is significantly greater in formulation F13 whose HLB is 14 (Fig 5).

Figure 5

3. This indicates that the HLB of the formulation plays a significant role in enhancing the solubility of the practically insoluble Lamotrigine.

4. All formulations achieve >75% release in 45 minutes in 0.1 N HCl which is the sink condition (Fig 6).

Figure 6

Table .

INTRODUCTION

Zileuton is an antiasthmatic [1][2][3][4] P a g e | 1562

Table . 1

INTRODUCTION

Green Tea is widely considered an A+ antioxidant due to its high concentration of polyphenols, which are compounds that help destroy potentially harmful free radicals.

Green tea significantly reduces the risk of death from many causes, including heart disease 1

OBJECTIVES OF THE STUDY

The objectives of this study were

RESULTS

Changes in Serum Total

Cholesterol Level Fig.1 and Table 1 imply that the Mean change in serum total cholesterol level in Group 1 was not significant and that of Group 2 was significant.

Figure 1

Table 1

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Fig.1. Changes in Serum Total Cholesterol Level

Changes in Serum LDL Level

There was decrease in serum LDL level in both Group 1 and 2. Fig.2 and Table 2 imply that the Mean change in serum LDL level in Group 1 was not significant and that of Group 2 was significant.

Figure 2

Table 2

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Fig.2. Changes in Serum LDL Level

Changes in Serum Triglyceride Level Fig.3 and Table 3 imply that the Mean change in serum triglyceride levels in Group 1 and Group 2 were not significant.

Figure 3

Table 3

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Fig.3. Statistical Representation of Changes in Serum Triglyceride Level

Changes in Serum HDL Level Fig. 4 and Table 4 imply that the Mean change in serum HDL level in both Group 1 and Group 2 was not significant.

Figure 4

Table 4

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Fig.4. Statistical Representation of Changes in Serum HDL Level

Table .

INTRODUCTION

Leucorrhoea or vaginal discharge is one of the very common problems or complaints 4 Bacterial vaginosis is termed vaginosis rather than vaginitis, because it is associated with alteration in normal vaginal flora rather than due to any specific inflammation.

MATERIALS AND METHODS

I.Oxidase Test:

To determine the presence of bacterial cytochrome oxidase is done by oxidation of the substrate,that is tetramethyl P-Phenylene diamine di hydrochloride to indophenol,which gives a dark purple coloured product. The dye is reduced to a deep purple colour.

Catalase Test :

This test demonstrate the presence of the catalse an enzyme that catalyses and release of oxygen from hydrogen peroxide.

Indole Test:

This test demonstrates the ability of certain bacteria to decompose the aminoacid tryptophane to indole, which accumulate in the medium containing sufficient tryptophane. Indole production is detected by Kovac's reagent.

4.Methyl Red Test:

The methyl red test is employed to detect the production of sufficient acid during the fermentation of glucose and maintenance of condition at the pH 4.5.

In the presence of the acid the test is positive, development of pink colour is noted. If the test is negative it will be yellow in colour.

Medium (Glucose

5.Voges-proskauer (Acetoin production)

Test:

Many bacterial ferment carbohydrates with the production of acetyl methyl carbinol (CH3 CO CHOH CH3) or its

Citrate utilization Test

This is a test for ability of an organism to utilize citrate is the sole carbon and· energy source for growth and ammonium salt as the sole source of nitrogen.

Table . I

Table . V

INTRODUCTION

All other ingredients, reagents and solvents were of analytical grade.

Methods

Drug loading (Pan Coating)

Step1: Weigh appropriate quantities of all the ingredients required for drug loading.

Step2: Take Povidone, IPA into tank, switch on homogenizer and mix for 10mins.

Step3: Load Milled Drug on to sugar spheres while spraying povidone solution in pancoater.

Step4: Unload the Drug loaded pellets from the pan & dry at specified temp for about 3 hrs (55 -65 C).

Step5: Load Milled sucrose onto dried pellets while spraying povidone solution & dry at specified temp for about 3 hrs (55 -65 C)

Polymer loading (Fluid Bed Coating)

Step1 Step2: Load HPMC P55 polymer solution and maintain the fluidization for 10 min.

Step3: Load Ethyl cellulose 7cps polymer solution and maintain the fluidization for 10 min.

EVALUATION PARAMETERS

The prepared pellets were evaluated for

DRUG RELEASE KINETICS:

Zero order release rate kinetics:

To study the zero order release kinetics the release rate data are fitted to the following equation

F=K0t

Here, F is the fraction of drug release K0 is the rate constant T is the release time

MATERIALS AND METHODS

Synthesis of 2-(dimethylamino)-N-[(2oxo-5-sulfamoyl-indolin-3ylidene)amino]acetamide (VIa)

. Percentage inhibition of edema was calculated using the formula given below and the results are presented in the Table 4.

Table 4

Mean edema of control group -Mean edema of treated group % inhibition of edema = Mean edema of control group X 100 Values (edema inhibition) represent mean values ± SD, n = 6.

Table .

INTRODUCTION

Hence asthma is a heterogeneous syndrome whose natural history is characterized by the variability in its symptoms and signs over time 2 .

Pharmacotherapy of asthma

A list of drugs used in pharmacotherapy of asthma is given in Table 2. P a g e | 1296

Table 2

. List of drugs in pharmacotherapy of Asthma nerve activity and reduces bronchial mucous secretion 9 . Since inhaled as an aerosol, it has a local action with delayed onset (30-60 min) of action. When dose of inhaled corticosteroids is doubled, it is found to be ineffective in preventing exacerbation of asthma. High dose inhaled corticosteroids administered at the onset of exacerbation increase the control of asthma 10 . Potential adverse effects associated with them such as oropharyngeal candidiasis,

INTRODUCTION

Experimental Work:

Nucleation assay

The classical model for the study of oxalate crystallization was chosen because of its simplicity and satisfactory reproducibility. 19 This model includes the study of

STRUCTURE OF DENDRIMER

Dendrimers are also known as arborols or cascade molecules are built from a starting atom, such as nitrogen, to which carbon and other elements are added by a repeating series of chemical reactions that produce a spherical branching structure.

As the process repeats, successive layers are added, and the sphere can be expanded to the size required by the investigator. The result is a spherical macromolecular structure whose size is similar to albumin and hemoglobin. For instance, 5th generation polypropylene imine is abbreviated to a "G5-PPIdendrimer".

Shell

The dendrimer shell is the homo-structural spatial segment between the focal points, the "generation space". The "outer shell" is the space between the last outer branching point and the surface. The "inner shells"

are generally referred to as the dendrimer interior.

Pincer

In dendrimers, the outer shell consists of a varying number of pincers created by the last focal point before reaching the dendrimer surface.

End-group

It is also generally referred to as the "terminal group" or the "surface group" of the dendrimer. Dendrimers having amine end-groups are termed "amino-terminated dendrimers".

PPI Dendrimer

These dendrimers are generally polyalkyl amines having primary amines as end groups, the dendrimer interior consist of numerous of tertiary trispropylene amines. PPI dendrimers are commercially available up to G5, and has found widespread applications in material science as well as in biology. P a g e | 1204

SYNTHESIS

PHARMACEUTICAL APPLICATIONS

Dendrimers as novel drug

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INTRODUCTION

Their individual and combined (interaction) effects in enhancing the dissolution rate and dissolution efficiency of piroxicam were evaluated in a 2 3 -factorial study.

MATERIALS AND METHODS

Materials

Methods

Preparation of Starch Citrate

Starch citrate was prepared based on the

Formulation of Piroxicam Solid

Preparation of the acetate buffer

To prepare the acetate buffer 0.385 gm of ammonium acetate and 0.5 mL of triethylamine were transferred into a1000 mL beaker and mixed with about 800 mL of milli-Q water. The contents were sonicated and the volume was made up to 1000 mL.

The pH of the solution was then adjusted to 4.5 with glacial acetic acid. It was then filtered through a 0.45µ membrane filter.

Preparation of the mobile phase

The optimized mobile phase consisted of a mixture of the above-mentioned acetate

RESULTS

Specificity

A good analytical method should be able to measure the analytes accurately in the presence of probable interferences from its solvent as well as from the excipients of its formulation. Figure 2 shows good chromatographic baseline separation of citalopram from its working standard solution. Figure 3 demonstrates that no interfering peaks were observed at the retention time of citalopram arising due to the excipients of its tablet.

Figure 2

Figure 3

Linearity

The calibration curve (n=3) constructed for the drug was linear over the concentration range of 25 -150 µg/mL. The regression of the plot was computed by least square regression method and is shown in Figure 4. The correlation coefficient is greater than 0.99 and the %RSD at each concentration studied was less than 2.

Figure 4

Available online: www.pharmanest.net (Table 3).

Table 3

Accuracy and precision

System suitability parameters

System suitability parameters were studied with six replicate injections of the standard solution and the results are presented in Table 4.

Table 4

Method suitability

The commercial tablet formulation, Celepra

Table . 1

INTRODUCTION

Fingolimod is an immunomodulating drug, approved for treating multiple sclerosis. It has reduced the rate of relapses in relapsing-remitting multiple sclerosis by over half, but has serious adverse effects.

MATERIALS AND METHODS

4-thiadiazole-2-amines (2a-h)

Table.2.Antibacterial activity of N-(p-substituted benzylidene)-5-propyl-1, 3, 4thiadiazole-2-amines

INTRODUCTION

Pre compression parameters:

Angle of repose:

Angle of repose is defined as the maximum angle possible between the surface of a pile of the powder and the horizontal plane. The flow characteristics are measured by angle of repose.

θ = tan -1 h/r

Where h = height of pile, r = radius of the base of the pile = angle of repose. P a g e | 1627

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Angle of repose below 25 0 indicates an excellent powder flow.

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Available online: www.pharmanest.net Table. 3. The results for angle of repose (θ)

Table

the uniformity of weight test prescribed in IP. The individual tablet weights when compared with average weight were within the official limit (±5%) of % deviation. The friability of immediate release tablets formulations were within the acceptable limits and ranged from 0.36-0.42%. All the evaluated parameters result obtained from different formulations of tablet is shown in

obtained was found to vary from 23.

Bulk density:

The bulk density of a powder is the ratio of the mass of an untapped powder sample and its volume including the part of the inter particulate void volume. It is expressed as gm/ml and calculated using the equation.

Ρ = W/Vb

Where Ρ = bulk density. W = mass of the powder blend. Vb = bulk volume of powder blend.

Tapped density:

Tapped density is the ratio of mass of powder to the tapped volume. It is calculated using the following equation and expressed as gm/ml.

Ρb, max = W/V50

Where Ρb, max = tapped density, W = mass of the powder blend.,V50 = volume of powder blend at 50 taps.

Carr's consolidation index:

It is defined as:

Hausner's ratio: It is defined as

METHOD

EVALUATION OF TABLETS

Tablet weight variation

Twenty tablets were randomly selected and accurately weighed and their average weight is calculated, such that each tablet weight should within the range of ± 5% .

Results are expressed as mean values ± SD.

Tablet hardness:

The Hardness of tablets was tested using Pfizer hardness tester.

Tablet thickness

A vernier caliper was used to determine thickness of 10 randomly selected tablets.

Results are Expressed as mean values

Drug content uniformity

Tablet friability

According to the BP specifications , 10 tablets were randomly selected and placed in the drum of a tablet friability test apparatus and rotated 100 times in 4 min at 25rpm. The percent weight loss was calculated for all formulation and was reported.

In-vitro Drug release studies:

Dissolution test was carried out using USP XXIV rotating paddle method (apparatus 2).

The stirring rate was 50 rpm. 6.8 p H buffer + Tween 80 were used as dissolution medium (900ml). It was maintained at 37 ± 1˚C. Samples of 5ml were withdrawn at Cross

ACKNOWLEDGEMENT

The Authors would like to thank Spectrum Pharma Ltd for providing facilities for pursuing the project.

CONCLUSION

The floating tablets of Candesartan Cilexetil were successfully formulated the bi layered tablets containing cross povidone, carbopol 934p (F12) showed satisfactory sustained drug release properties. The optimized formulation F12 followed zero order kinetic and the mechanism of drug release was found to be Higuchi mechanism.

Table .

INTRODUCTION

Cardiotoxicity is a condition arising due to extensive damage to the myocardium.

Hence, the heart may be unable to pump blood throughout the body. This can be due to the use of chemotherapy drugs and other medications. 1

Estimation of superoxide dismutase

The SOD activity was assayed by the method of Kakkaret al., (1984). The principle of the assay was based on the inhibition of nitrobluetetrazolium (NBT)

reduction. The reduction of nitro blue tetrazolium was inhibited by SOD, which was measured colorimetrically at 560 nm.

-One unit of SOD activity is defined as that amount of enzyme required to inhibit the reduction of NBT by 50% under the specified conditions‖. 9 P a g e | 1135

Estimation of Lipid peroxidation

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INTRODUCTION

In very early history, the children were literally excluded from medical discussions.

UNITED STATES LEGISLATION

Globally, the first initiation for regulating paediatric medicines was made by the US.The major regulatory milestones for paediatric drugsare provided in Table 2.

Table 2

.Major milestones and highlights in Paediatric regulations of the US Cosmetic Act)is voluntary for the sponsor. The provisions apply to both new drugs/biologics, drugs already on the market and also for off patent drugs. Under generics of the product and is known as Paediatric exclusivity. Paediatric exclusivity can only be granted to those products that are "on-patent" that is, those that have patent protection.To qualify for paediatric exclusivity, the paediatric studies must also satisfy the requirements PREA under section 505A of the act 16 .Paediatric Review Committee (PeRC) will review all written requests and reviews studies submitted by sponsor under the section 505A of FFDCA (Federal Food Drugs and Cosmetics Act) and make a recommendation on exclusivity determinations 17 . applications. Once the IND is reviewed, sponsor may initiate the clinical trials 15, 16 . The results of paediatric studies conducted under PREA and BPCA are submitted to FDA in an application as New Drug Application (NDA) or supplemental NDA. experiences in the US, a similar approach is made in Europe in 2007. In the EU, legislation is unified and there is only one, whereas in the USit is regulated by two laws. During the period of 1998 to present, many studies were conducted that resulted in new paediatric labeling. The new labels include important new information regarding safety and effectiveness in dosing/pharmacokinetics. Compared to initial years of regulation, paediatric R&D and the number of companies that utilized free scientific advice also have increased. It is also worth mentioning here that the development of off-patent medicines through funding Available online: www.pharmanest.net program and number of exclusivities also has increased which reflects the industries approach towards paediatric medicine development. In the EU, total scientific advice requests are 332 and total protocol assistance requests are 68.The US paediatric plan of PREA is comparable to EU PIP, where both outline the design of paediatric studies. Both the EU and US legislations include facilitating measures in form of waivers and deferrals. The main driving force and attractive reward is the 6-months extension of patent if it satisfies the conditions of EU PIP and written request (WR) of the FDA. Health Canada also offers a similar supportive measure of 6 months patent extension. But this is applicable only to drugs under patent protection. This attracts an innovator, by recovering the cost of testing through the 6 month patent extension but may impact the generic drug firms for loss of revenues. The number of paediatric exclusivities granted in EU during 2000 and 2010 are shown in

PHARMANEST -An International Journal of Advances in Pharmaceutical Sciences

Table .

EXPERIMENTAL METHODS

Preparation of Standard solutions

Stock solutions for measurements were P a g e | 1125

PHARMANEST -An International Journal of Advances in Pharmaceutical Sciences

Selection of mobile phase

A trial and error process was done to select the appropriate mobile phase. The solvent system of Toluene: Ethyl acetate:

DMF in the ratio 6.5: 3.0: 0.5 was the most appropriate solvent system for the HPTLC analysis of cilnidipine and telmisartan in methanol.

Application of standard solutions

Separate fig.(1) and (2) and (3) respectively. The peak areas and peak heights were noted. where y is response and x the amount chromatographed. The correlation coefficients r, were 0.9917 and 0.9852 respectively, over these concentration ranges. The data is given in Table 1 and Table 2. Available online: www.pharmanest.net substituting values in the regression equations as given above. (Table 3) The values prove that the method is accurate.

Figure 1

intermediate precision for the proposed method was determined by estimating standard solution of cilnidipine and telmisartan for three different concentrations for three times on the same day(intraday) and on three different days(interday). The results are reported in terms of relative standard deviation (RSD).

Table 1

. Rf factor, height and area of Cilnidipine peak

Table 3

.Summary of validation parameters for the proposed methods

Development of spot

Method Precision (Repeatability)

The precision of the instruments was checked by repeatedly scanning (n = 6) standard solutions of cilnidipine and telmisartan (100 μg/ml). The RSD values were found to be below 2% which indicate that the proposed methods are repeatable.

( Table 3).

Intermediate Precision (Reproducibility)

The The RSD values were found to be below 2% which indicate that the proposed methods are reproducible ( Table 3).

Limit of detection (LOD) and limit of quantification (LOQ)

LOD and the LOQ of the drug were calculated using the following equations as per International Conference on Harmonization (ICH) guidelines.

LOD = 3.3 X Std.deviation/Slope,and LOQ = 10 X Std.deviation /Slope

The data are provided in Table 3.

P a g e | 1129

Table .

INTRODUCTION

Among the various ecosystem on earth, soil is considered to be the richest source of native microbes observed in terrestrial environment. A number of commercially useful enzymes including proteases have been traditionally produced using microbes isolated from soil. Each environment has its own unique characteristics and hence there is a wide difference in microbial diversity observed at various localities 1 . Microbes distributed in the soil, produces a number of extracellular enzymes which mainly helps microorganism to breakdown complex organic matter into their simplest form. This helps microbes to meet their nutritional requirements 2 . Rapid change in the climate along with urbanization and change in agriculture practices affects microbial population observed at a particular location. Therefore, microbial diversity changes over a time with respect to the changing flora and fauna. Even in case of under reported records it is observed that there are at least 10 8 -10 10 microbes present in 1 g of soil. Therefore there is always a possibility that the number of microorganisms found in a given sample of soil will far exceed the expected limit. Microbes found in natural habitat constantly try to evolve so that they are able to produce extracellular enzymes spending the least possible energy. Hence, through traditional screening method and natural selection it is possible to isolate potential microorganisms that could be useful at industrial level 3,4

MATERIALS AND METHODS

Chemicals and Reagents

Optimization of cultural conditions

Protease yield of KWF-2 was improved through cultural condition optimization by one-factor-at -a-time design (OFAT).

Assay of protease

RESULTS FOR BIOLOGICAL ACTIVITIES

Primary screening

Proteolytic activity of KWF2 was far higher than the other isolates ( Table 2).

Table 2

Table.2.Protease activity of the isolates

Among the isolates obtained during screening, KWF-2 showed the highest activity with zone of activity being 2.9 cm (Fig. 1). showed the least activity with zone of activity being 0.3 cm. Since prominent proteolytic activity was observed for KWF-2 among the isolates tested, they were selected for optimization studies.

Figure 1

Isolate Protease activity (zone of activity in cm)

Tyrosine standard curve

A series of tyrosine concentration was prepared and its absorbance was measured ( Fig. 2). Available online: www.pharmanest.net

Figure 2

Glucose-Yeast extract medium was used as inoculation medium. Growth from a 10 day old slant was transferred to inoculation

Optimization of growth conditions

The type and yield of protease is known to be highly dependent on pH of the production medium. Therefore, the effect of initial pH of the production medium on protease production by KWF-2 was evaluated. The study showed that enzyme yield was better in alkaline conditions.

There was appreciable fall in enzyme yield under acidic conditions especially below pH 5.0. Among the various pH tested, maximum yield was observed at pH 9.0. At pH 9.0, amount of tyrosine released was 52.4mg, while with pH 3 it was observed to be 22.7 mg (Fig. 3). Under alkaline conditions the protease yield was better.

Figure 3

Fig.3.Effect of initial production medium pH on protease yield

The study on effect of nutrient supplementation showed that among the various carbon sources tested on protease production, dextrose at 1% w/v increased enzyme yield compared to other carbon sources (Fig. 4).

Figure 4

Available online: www.pharmanest.net

Fig.4.Effect of carbon supplements on protease yield

A combination of Mg 2+ and Ca 2+ at concentration of 0.1 and 0.01% w/v respectively improved protease yield (Fig. 5). Aspergillus tamari has been reported to produce maximum amount of alkaline protease when grown on a medium with initial pH 9.0 8, 9 . This shows that protease from KWF-2 is an alkaline protease.

Figure 5

Fig.5.Effect of metal ions

Alkaline proteases are useful in tanning, leather and detergent industries. Calcium plays an important role in increasing the protease yield. In organism such as B.

cereus and B. licheniformis, Ca 2+ is reported to increase the protease yield significantly.

In case of P. aeruginosa, addition of either calcium or magnesium causes significant increase in protease production. This could be due to the role of calcium in maintaining conformational structure 10-13 .

Taxonomy of Cissus Quadrangularis

Besides the usual botanical classification,

Plant Parts Used

The whole plant used specially leaves, roots and stem.

Monographs

Bengali Names : Hadjod, Harbhanga One gram of the extract was dissolved in few drops of dry acetic acid, 3 ml of acetic anhydrade was added followed by few drops of conc sulphuric acid. Appearance of bluish green colour showed the presence of phytosterol.

Test for Fixed oils and Fats

A small quantity of the extracts was separately pressed between two filter papers. Appearance of oil stain on the paper indicates the presence of fixed oil. In the assessment and evaluation of the

ORIGIN OF THE ECHINOCANDINS

Presumably, the side-chain intercalates with the phospholipid bilayer of the cell membrane.

Caspofungin (acetate) is freely soluble in water, methanol and slightly soluble in ethanol.

Micafungin is freely soluble in water whereas anidulafungin is not ( Figure 1) Available online: www.pharmanest.net

Figure 1

MECHANISM OF ACTION OF ECHINOCANDINS

ADVERSE EVENTS AND TOXIC EFFECTS

Headache is a frequent side-effect with all three compounds. Local irritation at the infusion site, fever, liver toxic effects-rise in alanine aminotransferase, patchy hepatic necrosis, abnormal liver-function seen more with patients receiving caspofungin.

Histamine-like reactions are seen after rapid anidulafungin administration.

ADVANTAGES OF ECHINOCANDINS:



Preparation of mobile phase

A 10 mM phosphate buffer was prepared by

Method-III (RP-HPLC):

The HPLC system was stabilized for thirty min. by following the chromatographic conditions as described in Table 1

Table 1

RESULTS AND DISCUSSION

Table no .

Table . 1

INTRODUCTION

Retention of drug delivery system in the In the present study, an attempt was made to develop gastro retentive floating drug

METHODS

Drug-Excipient compatibility Studies

FT-IR 8 :

The infrared spectra of Acyclovir, physical mixture of drug and Excipient which were recorded between 400 to 4000 cm-1 on FTIR. The IR spectra for the test samples were obtained using KBr disk method using an FTIR spectrometer.

Formulation of Acyclovir

Available online: www.pharmanest.net

In vitro buoyancy studies:

The results for floating time are presented in Table 7. From the study of floating properties, it was observed that the floating lag time ranges from 2 seconds to 12 minutes and remained buoyant up to more than 12 hours.

Table 7

In vitro drug release studies:

Preparation of extract

The root of the plant were shade dried and made into coarse powder. It was extracted with aqueous ethanol in a Soxhlet apparatus for 72 hours. The concentrated material was reduced to a thick mass at room temperature and water was removed by placing it on water bath. The weight of the dried material was recorded and used for experimental study 8.

Experimental animals

Albino Wistar rats (180-230 g) of either sex were fed with a standard diet and water ad

INTRODUCTION

Microbes practically can produce any molecule 1

Characteristic of the colonies isolated

All the isolates were preserved on agar slants (Nutrient agar for bacterial and Potato dextrose agar for fungal) and then subcultured regularly.

The isolates were then subjected to biological studies viz., amylase activity and antimicrobial activity. The results of these studies are tabulated and given below.

RESULTS FOR BIOLOGICAL ACTIVITIES

Primary screening

Of all the isolates tested for amylase activity, six isolates showed positive result for amylase activity (Table 2). Among these isolates, KWF-2 showed the highest activity with clear zone of activity being 2.5 cm (Fig. 1), where as the isolate MC1 showed the least activity with a diameter of 0.2 cm.

Table 2

Figure 1

Amylase activity of KWF2 . KWF-2 showed clear zone during primary screening for antibiotic activity. Therefore, KWF-2 was further studied. The isolate was grown on Sabouraud dextrose medium and supernatant was tested for antimicrobial activity by agar diffusion method. Among all the isolates tested for antimicrobial activity,

KWF-2 which through gross morphological study was identified as yeast, showed good amylolytic activity. Therefore it was selected for further studies. against Bacillus subtilis shown in (Fig. 2).

Figure 2

There was very little antimicrobial activity seen against other microorganisms. The standard drug used for comparison was Ciprofloxacin.

Fig.2.Isolate KWF-2 showing antimicrobial activity against Bacillus subtilis

Table .

INTRODUCTION

In the recent years of development in pharmaceutics, increasing attention is being given for administering drugs in a more challenging and controlled manner for better therapeutic end point 1,2 . Oral ingestion has long been the most convenient and commonly employed route of drug delivery due to its ease of administration, high patient compliance, least sterility constraint and flexibility in the design of the dosage form. The goal of any drug delivery system is to provide a therapeutic amount of the drug at the target site in the body and maintains the desired drug concentration for prolong period of time. Over the past decade an entirely new technique for the delivery of a drug and other biologically active agents has been developed.

Sustained release (SR) has given a new breakthrough for novel drug delivery system in the field of Pharmaceutical technology. They are also referred to as "long acting" or "delayed release" when compared to "rapid" or "conventional" release preparations. Sustained release (SR) formulations offer many potential advantages, such as sustained blood levels, Pre-compression studies of Sustained Release tablets:

Bulk density:

Bulk density is the ratio of total mass of powder to the bulk volume of powder. It was measured by pouring the weight powder (passed through standard sieve #20) into a measuring cylinder and initial weight was noted. This initial volume is called the bulk volume. It is expressed in g/ml and is given by

Bulk density (Db) = Mass of powder(M)/ bulk volume of powder(Vb)

Available online: www.pharmanest.net Tapped Density:

It is the ratio of the total mass powder to the tapped volume of the powder. It was determined by placing a graduated cylinder, containing a known mass of drug-excipient blend. The cylinder was allowed to fall under its own weight onto a hard surface from the height of 10cm. The tapping was continued until no further change in volume was noted.

Dt= M / Vt

Where, M is the mass of powder Vt is the tapped volume of the powder.

Angle of Repose :

It is defined as, the maximum angle possible between the surface of the pile of the powder and the horizontal plane. The angle of repose was determined by the funnel method suggested by

Newman. Angle of repose is determined as

Tan θ = h/r

Therefore θ = Tan -1 h/r

Where, θ = Angle of repose, h = height of the cone, r = Radius of the cone base.

Compressibility Index :

It is an indirect measure of bulk density, size, shape, surface area, moisture content and cohesiveness of materials because all of these can influence the observed compressibility index.

Carr's compressibility index (%) = [(Dt-Db) X

100] / Dt

Where, Dt is the tapped density Db is the bulk density Hausner's ratio: Tapped density and bulk density were measured and the Hausner"s ratio was calculated using the formula,

Hausners ratio = ρt / ρo

Where, ρt = Tapped density ρo = Bulk density

Post compression parameters:

Weight variation test :

The weight variation test is carried out in order to ensure uniformity in the weight of tablets in a batch. The total weight of 20 tablets from each formulation was determined and the average was calculated. The individual weights of the tablets were also determined accurately and the weight variation was calculated. Carvedilol phosphate release from the formulated tablets was slow and spread over 24 h and depended on percent polymer in the tablet. Fickian diffusion was the drug release mechanism from the formulated tablets. Carvedilol phosphate release from matrix tablets F3 formulated employing 20 % cross carmellose sodium was similar to that from COREG Tablets, a commercial controlled release formulation of Carvedilol phosphate. Drug-excipient interaction and stability studies were carried out and was observed that there was no interaction.

Crosscarmellose sodium polymer is suitable for the design of oral sustained release tablets.

Table

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