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Friedel-crafts alkylation on mesoporous W-Zr composite oxide catalysts prepared by a wall ionexchange method

Shirisha N*, Md Fazal UI Haq S

Department of Pharmaceutical Sciences, Institute of Science and Technology, JNTUH, Hyderabad, Telangana, India

*Corresponding Author:
N Shirisha,  Department of Pharmaceutical Sciences, Institute of Science and Technology, JNTUH Hyderabad, India   E-mail: [email protected]

Received: 18-Feb-2022, Manuscript No. 22-49421; Editor assigned: 21-Feb-2022, Pre QC No. JPN-22- 49421 (PQ); Reviewed: 7-Mar-2022, QC No. JPN-22- 49421; Accepted: 11-Mar-2022, Manuscript No. JPN-22- 49421 (A); Published: 18-Mar-2022, DOI: 10.4172/2347-7857.10.2.006.

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The wall ion-exchange (WIE) method, in which wall anions in composites of zirconium sulfate and surfactant micelles (ZS) were exchanged for oxyanions in aqueous solutions, was applied to prepare mesoporous tungsten-zirconium composite oxide (WZO). The amounts of tungsten introduced into the ZS structure (Win) were very small at pH=2-5 and greatly increased at pH=5.6 and above. In the exchange at pH=5.6-10, the ratios of tungsten introduced and sulfur removed were 0.9-1.1, indicating the stoichiometric ion-exchange. This would result from the difference of predominant tungsten oxyanions in the solutions, W12O39 6- (the diameter, 0.7 nm) at the low pH and WO4 2- (0.27 nm) at high pH, since the diameter of the latter is very similar to that of the HSO4- ion (0.21 nm) in ZS, resulting in the easy WIE reaction. The relationships among the amount of Win, the removal method of the surfactants, the surface area and the pore diameter of WZOs were systematically studied and WZO samples with high surface areas of 200-520 m2 g-1 and pore diameters of 0.8-2.4 nm could be prepared. The catalytic activity of the resulting WZO for the Friedel-Crafts alkylation was strongly dependent on the removal method of the surfactants and the W/Zr ratio. Alkylation is the trading of an alkyl pack beginning with one molecule then onto the following. The alkyl social event may be moved as an alkyl carbocation, a free radical, a carbanion or a carbene (or their equivalents). An alkyl pack is somewhat of a molecule with the general condition CnH2n+1, where n is the entire number outlining the amount of carbons associated together. For example, a methyl gathering (n = 1, CH3) is a piece of a methane iota (CH4). Alkylating authorities use specific alkylation by including the perfect aliphatic carbon chain to the as of late picked starting molecule. This is one of many known substance amalgamations. Alkyl social events can in like manner be removed in a strategy known as dealkylation. Alkylating administrators are normally orchestrated by their nucleophilic or electrophilic character.  In oil refining settings, alkylation insinuates a particular alkylation of isobutane with olefins. For updating of oil, alkylation conveys a phenomenal blending stock for gasoline. In prescription, alkylation of DNA is used in chemotherapy to hurt the DNA of harmful development cells. Alkylation is rehearsed with the class of prescriptions called alkylating antineoplastic administrators. Nucleophilic alkylating experts pass on what may be contrasted with an alkyl anion (carbanion). The formal "alkyl anion" attacks an electrophile, molding another covalent bond between the alkyl gathering and the electrophile. The counterion, which is a cation, for instance, lithium, can be ousted and tidied away in the work-up. Models join the usage of organometallic blends, for instance, Grignard (organomagnesium), organolithium, organocopper, and organosodium reagents. These blends generally can add to an electron-deficient carbon atom, for instance, at a carbonyl social occasion. Nucleophilic alkylating masters can oust halide substituents on a carbon bit through the SN2 part. With a catalyst, they moreover alkylate alkyl and aryl halides, as exemplified by Suzuki couplings. N-and P-alkylation are critical strategies for the advancement of carbon-nitrogen and carbon-phosphorus securities. Amines are speedily alkylated. The pace of alkylation follows the solicitation tertiary amine < discretionary amine < fundamental amine. Common alkylating administrators are alkyl halides. Industry as often as possible relies upon green science procedures incorporating alkylation of amines with alcohols, the symptom being water. Hydroamination is another green method for N-alkylation. In the Menshutkin reaction, a tertiary amine is changed over into a quaternary ammonium salt by reaction with an alkyl halide. Practically identical reactions happen when tertiary phosphines are treated with alkyl halides, the things being phosphonium salts. Thiols are promptly alkylated to give thioethers. The response is commonly directed within the sight of a base or utilizing the conjugate base of the thiol. Thioethers experience alkylation to give sulfonium particles. At the point when the alkylating operator is an alkyl halide, the change is known as the Williamson ether union. Alcohols are additionally acceptable alkylating operators within the sight of reasonable corrosive impetuses. For instance, most methyl amines are set up by alkylation of alkali with methanol. The alkylation of phenols is especially direct since it is   dependent upon less contending responses. Electrophilic alkylating operators convey what might be compared to an alkyl cation. Alkyl halides are ordinary alkylating specialists. Trimethyloxonium tetrafluoroborate and triethyloxonium tetrafluoroborate are especially solid electrophiles because of their plain positive charge and an inactive leaving gathering (dimethyl or diethyl ether). Dimethyl sulfate is middle of the road in electrophilicity. Electrophilic, dissolvable alkylating operators are frequently harmful and cancer-causing, because of their propensity to alkylate DNA. This system of poisonousness is applicable to the capacity of against malignant growth drugs through alkylating antineoplastic specialists. Some synthetic weapons, for example, mustard gas work as alkylating specialists. Alkylated DNA either doesn't loop or uncoil appropriately, or can't be handled by data unraveling compounds. In a customary petroleum treatment facility, isobutane is alkylated with low-atomic weight alkenes (fundamentally a blend of propene and butene) within the sight of a Brønsted corrosive impetus, which can incorporate strong acids (zeolites). The impetus protonates the alkenes (propene, butene) to deliver carbocations, which alkylate isobutane. The item, called "alkylate", is made out of a blend of high-octane, spread chain paraffinic hydrocarbons (for the most part isoheptane and isooctane). Alkylate is a top notch gas mixing stock since it has uncommon antiknock properties and is perfect consuming. Alkylate is additionally a key segment of avgas. By consolidating liquid synergist splitting, polymerization, and alkylation treatment facilities can acquire a gas yield of 70 percent. The across the board utilization of sulfuric corrosive and hydrofluoric corrosive in processing plants presents noteworthy natural dangers. The WZO samples prepared with calcination or extraction showed low activity for the catalysis, while the extracted and then calcined WZOs with W/Zr>0.45 were specifically active. The activity was well proportional to the amount of mono-dentate W species produced in the pore surface of the WZO samples.


Niosome; entrapment efficiency; sustained release; skin penetration


Niosomes are bilayered microscopic lamellar structures with a size range between 10-10000 nm. They are formed by self-association of non-ionic surfactants in aqueous phase. They are spherical in shape and consists of lamellar (unilamellar and multilamellar) structures. Encapsulation of the drugs in niosomes improves the drug permeation. They can encapsulate both hydrophobic and hydrophilic drugs. Hydrophilic drugs can be delivered by adsorbing on the surface of the bilayer or by entrapping the drug in aqueous core of particle, hydrophobic drugs are delivered by encapsulating the drug into bilayer of non-ionic surfactants. Niosomes are composed of non-ionic surfactants, lipids and polymers where surfactants act as penetration enhancers and lipids are used to provide rigidity and proper shape [1]. Niosomes are obtaining much attention because of their advantages like physical and chemical stability, content uniformity, low cost, convenient storage and various surfactants are available forniosomal formulations. A Niosomal formulation minimizes drug degradation, inactivation of drug after administration and prevents side effects. Niosomal gel formulations are used in treatment of various diseases like arthritis, gout, psoriasis and antifungal infections [2].

Materials And Methods

Mefenamic acid, Cholesterol, span 20, span 80 and Carbopol 940 from research lab, Preparation of mefenamic acid niosomes: Mefenamic acid niosomes were prepared by thin film hydration method by using two different surfactants (span 20 and span 80). A mixture of either span 20 or span 80 and cholesterol are weighed accurately and then the accurately weighed amount of drug was added to the lipid mixture [3]. All ingredients were then dissolved in 10 ml of methanol and then organic solvent was removed by the rotary evaporation under reduced pressure on a water bath at 60°C. Then the deposited film was then hydrated with 10 ml of phosphate buffer of pH 7.4. Preparation of Niosomal gel 1.5 g of carbopol 940 powder was dispersed into 10 ml of water and vigorously stirred and allowed to hydrate for 24 hrs. Then the dispersion was neutralized with triethanolamine to adjust pH (6.8). Appropriate amount of niosomes containing mefenamic acid was then incorporated into gel base with continuous stirring until homogenous formulation was achieved [4].

Table 1. Composition of different Niosomal aqueous dispersion.

Ingredients (mg) MA1 MA 2 MA3 MA 4 MA 5 MA 6 MA 7 MA 8 MA 9 MA 10
Mefenamic acid 100 100 100 100 100 100 100 100 100 100
Span 20 100 -- 150 -- 200 -- 250 -- 300 --
Span 80 -- 100 -- 150 -- 200 -- 250 -- 300
Cholesterol 50 50 50 50 50 50 50 50 50 50
Methanol 20 20 20 20 20 20 20 20 20 20
Phosphate Buffer Qs Qs Qs Qs Qs Qs Qs Qs Qs Qs

Evaluation of niosomal gel

Formulated gel was evaluated for their physico-chemical properties, in-vitro release studies and Drug content and drug entrapment studies [5].

Clarity: The clarity of various formulations was determined by visual inspection under black and white background [6].

Measurement of pH: The pH of mefenamic acid gel formulation was determined by using digtal pH meter 1gram of gel was dissolved in 100 ml of distilled water. The measurement of pH of each formulation was done in triplicate and average values were calculated [7].

Homogeneity: All developed gels were tested for homogeneity by visual inspection after the gels have been stored in the container for their appearance and presence of any aggregate [8].

Rheological Characterization: The rheological studies of samples were carried out with Brookfield Digital viscometer (LV DV-E model) using S-18 spindle number [9,10]. The developed formulations were poured into the small sample adaptor of the Brookfield viscometer and the angular velocity increased gradually from 0.5 to 100 rpm.

Drug content: Niosomes equivalent to 20 mg were taken into a standard volumetric flask. They were lysed with 25 ml of methanol by shaking for 15 min [11]. The clear solution was diluted to 100 ml with methanol. Then 10 ml of this solution was diluted to 100 ml with phosphate buffer 6.8. Aliquots were withdrawn and the absorbance was measured at 285 nm and drug content was calculated from the calibration curve [12].

The drug content was determined by using following equation

Drug content=(concentration× volume taken) × conversion factor

Scanning Electron Microscopy: Scanning Electron Microscopy (SEM) is used to determine the surface morphology of niosomal gel with polymer (roundness, smoothness and formation of aggregates).

Entrapment Efficiency: To 0.5 g of niosomal gel weighed in a glass tube, 10 ml of the aqueous phase (phosphate buffer pH 6.8) were added; the aqueous suspension was then sonicated [13]. Niosomes containing. Mefenamic acid were separated from unentrapped drug by centrifugation at 9000 rpm for 45 min at 4°C. The supernatant was recovered and assayed spectrophotometrically using Shimadzu UV spectrophotometer at 285 nm. The encapsulation efficiency was calculated by the following equation [14.15].

% Encapsulation efficiency=(amount of entrapped drug/total drug added) *100

In vitro diffusion studies: The in vitro diffusion study of prepared gel was carried out in Franz diffusion cell using through an egg membrane. 14 ml of phosphate buffer was taken in as receptor compartment, then 1 gm Mefenamic acid gel was spread uniformly on the membrane. The donor compartment was kept in contact with a receptor compartment and the temperature was maintained at 37±0.50°. The solution on the receptor side were stirred by externally driven Teflon coated magnetic bars at predetermined time intervals, pipette out 5 ml of solution from the receptor compartment at specified time intervals for up to 24hrs and immediately replaced with the fresh 5 ml phosphate buffer. The cumulative % release of drug was calculated against time [16].

Stability study: To determine the stability of the formulation one should first know the stability of the drug and the vesicles, studies were carried to evaluate total drug content at room temperature (27±2°C) and refrigeration temperature (4±2°C).samples was collected for every 2 weeks and absorbance was seen at 285nm in U.V spectrometer.

Results And Discussion

Solubility studies

The solubility of drug in the water was found to be insoluble and slightly soluble in ethanol. Better solubiliry was found to be in methanol.

Table 2. Table showing the Solubility of Mefenamic acid (API) in various solvents.

Solvents Solubility
Water Insoluble
Methanol Soluble
Ethanol Slightly soluble

Fourier transforms infrared study

FT-IR Spectrum of pure drug- mefenamic acid


Figure 1. FT-IR Spectrum of pure drug-mefenamic acid in kbr.

FT-IR Spectrum of Mefenamic acid and Cholesterol


Figure 2. FT-IR spectra of mefenamic acid and cholesterol.

FT-IR Spectrum of mefenamic acid and span 20


Figure 3. FT-IR Spectra of mefenamic acid and span80.

FT-IR Spectrum of mefenamic acid and span 80


Figure 4. FT-IR Spectra of mefenamic acid and span80.

Size and shape analysis: Microscopic analysis was performed under different magnification to visualize the vesicular structure, lamellarity and to determine the size of niosomal preparations.

Scanning electron microscope


Figure 5. Scanning electron microscopes and Optimized niosomal gel.


Figure 1: journal-pharmaceutics-niosomal-10-3-421-g005

Entrapment efficiency: Once the presence of vesicles was confirmed in the Niosomal system, the ability of vesicles for entrapment of drug was investigated by ultra-centrifugation. Ultra-centrifugation was the method used to separate the Niosomal vesicles containing drug and un-entrapped or free drug, to find out the entrapment efficiency. The maximum entrapment efficiency of Niosomal vesicles was determined by ultracentrifugation.

Drug content: Drug content of niosomal formulations were determined. The results obtained shows 93.18- 97.82% drug content in the formulations. The results obtained are shown in table 3.

Table 3: % Drug entrapped and % Drug content in niosomes.

Formulation % Entrapment Efficiency % Drug content
MA1 81.12±0.32 93.18±1.52
MA2 82.42±1.2 94.20±0.91
MA3 81.28±0.54 94.19±0.74
MA4 83.19±0.23 94.28±1.15
MA5 89.16±0.71 97.82±0.51
MA6 89.48±0.81 97.27±0.81
MA7 89.16±0.45 96.64±1.41
MA8 86.43±1.21 96.12±1.32
MA9 88.74±1.28 96.28±1.11
MA10 89.46±0.71 96.78±1.31

Clarity: Niosomes containing gels were found to be sparkling and transparent were found to be translucent and white viscous. All gels were free from presence of particles

PH value: The value of pH of topical Niosomal gels was measured by using digital pH meter at the room temperature. The pH of all topical Niosomal gels was found to be in the range of 6.5 ± 0.03 to 6.8 ± 0.02.

Homogeneity: All developed (MA1, 3, 4, 5, 6, 8, 9 , 10) showed good homogeneity with absence of lumps. The developed preparations were much clear and transparent.

Viscosity measurement: The viscosity of various formulated Mefenamic acid gels was measured using a Brookfield viscometer. The rheological behavior of all formulated gels systems was studied. In gel system, Consistency depends on the ratio of solid fraction, which produces the structure to liquid fraction. Viscosity of various formulated gels was found in range of 1760 to 2120 centipoises.

In vitro drug diffusion studies: In vitro drug release studies were carried out on dissolution test apparatus Franz diffusion cell. These release studies revealed that, the order of release was found to be.

Table 4. Viscosity of the developed gel.

Formulation code Viscosity(cps)
MA1 1760
MA2 1783
MA3 1756
MA4 1794
MA5 2120
MA6 1953
MA7 1908
MA8 1819
MA9 1810
MA10 1698

Table 5. In-Vitro drug release of niosomal gel formulations.

Time in hrs MA1 MA2 MA3 MA4 MA5 MA6 MA7 MA8 MA9 MA10
0 0 0 0 0 0 0 0 0 0 0
1 3 2.5 5.3 4.1 6.5 5.5 4.8 3.4 3.8 2.7
2 6.5 4.1 10.5 9.9 16.5 7.3 10.5 9.9 10.8 8.8
3 8.2 9.7 17 12.9 25.1 9.8 12.4 14.7 14.9 16.9
4 12.4 15.2 21.6 18.5 33.1 12.3 18.8 21.4 24.9 20.6
5 18.5 29.7 32.9 28.4 41.6 24.8 26.7 30 32.4 28.7
6 28.4 45.7 48.7 38 53.2 30.6 35.2 32.9 40.5 35.1
8 35.9 50.6 61 48.9 67.5 42.7 46.8 38.8 49.2 47.2
12 41.3 55.7 78.2 67.2 80.2 55.3 58 48.7 57 52.7
24 52.8 60.7 86.3 75.2 95.7 79.3 83.5 69.2 73.2 61.1

Figure 7. Graph showing in vitro drug release for niosomal formulations.

Based on the mefenamic acid nisomal gel drug release MA5 showed maximum drug release 95.7% upto 24hrs it was selected as optimized formulation

Stability studies

Table 6. Loss in percentage drug during stability studies.

Formulation code (MA5) Percentage of drug release
Initial 4±2 ° C 96.3
27±2 ° C 96.2
After 2 weeks 4±2 ° C 96.6
27±2 ° C 96.1
After 4 Weeks 4±2 ° C 95.9
27±2 ° C 95.5
After 6weeks 4±2 ° C 94.9
27±2 ° C 94.4
After 8 weeks 4±2 ° C 94.5
27±2 ° C 94.2


Recently derived Niosomal system can deliver drug molecules into and through the skin. In the present study an attempt was made to formulate and evaluate Niosomal system of Mefenamic acid. Estimation of mefenamic acid was done in methanol spectrophotometrically at 285nm. Niosomes were prepared by thin film hydration method and are evaluated for their appearance, pH, drug content, rheological properties, drug entrapment study and in-vitro release. Visually gels were sparkling and transparent. Promising results were obtained with MA5 formulation containing Span 80 and cholesterol because of the highest entrapment efficiency and high localization in the stratum corneum than the Span 20. However Niosomes prepared by thin film hydration method were more uniform and small in size which is essential for skin penetration. The invitro drug release revealed the formulations followed by slow sustained release of the drug for 24 h.