Solubility Of Furosemide Research Articles

The use of Cyclodextrin-SLS-PEG 4000 Complex to Solubilize Three BCS Class II and IV Drug´S through A Factorial Study Design

Objective: Drugs classified as Class II and IV on the Biopharmaceutical Classification System are commonly associated with solubility challenges. This research aims to investigate the impact of cyclodextrin combined with both PEG 4000 and SLS, individually and in combination, on the enhancement of solubility and dissolution rate of three drugs belonging to BCS Class II (celecoxib and Valsartan) and Class IV (Furosemide). Methods: A series of 23 factorial experiments were conducted to assess drug solubility in eight selected fluids containing Beta Cyclodextrin, Poly Ethylene Glycol 4000, Sodium Lauryl Sulphate, both separately and in binary and ternary combinations. Solid inclusion complexes of each drug with beta Cyclodextrin, PEG 4000 and SLS were prepared using the kneading method. The impact of each excipient on dissolution rates was evaluated through a23 factorial design. Results: The presence of the studied excipients significantly improved the solubility of the three drugs under investigation. Celecoxib solubility was highly enhanced by Cyclodextrin combined toPEG 4000 and SLS(2,77 ratio). Furosemide solubility was highly enhanced by Cyclodextrin combinedto SLS (ac) (2,96 ratio). And valsartan solubility by beta cyclodextrin combined to PEG 4000 and SLS(2,43 ratio). Among dissolution rates, the addition of PEG 4000 and SLS alongside Cyclodextrin led to even more substantial improvements: 14.96-ratio and 7.34-ratio enhancements, respectively on celecoxib dissolution rates, and 9,22-ratio and 11,73-ratio increases, respectively, for furosemide dissolution rates, then.2,09-ratio and 1,88-ratio, respectively on valsartan dissolution rates. Conclusion: Sodium Lauryl Sulphate demonstrates efficacy as a solubilizer both independently and in conjunction with ßCD and PEG 4000, effectively enhancing the solubility and dissolution rate of the selected BCS Class II and IV drugs.

Preparation and Characterization of Furosemide Solid Dispersion with Enhanced Solubility and Bioavailability.

Furosemide (FMD), as a potent circulating diuretic, is commonly used for the treatment of hypertension and edema arising from cardiac, renal, and hepatic failure. However, the low solubility of furosemide restricts its dissolution and bioavailability. In this study, Polyvinylpyrrolidone K30 (PVP-K30), mesoporous (Syloid 244FP, Syloid XDP 3050), and non-mesoporous (Aeroperl 300, Aerosil 200) silica were chosen as combined carrier to develop novel amorphous solid dispersions of furosemide, and then its dissolution and bioavailability were evaluated. Characterization study included XRD, DSC, TGA, SEM, FT-IR, and molecular docking. We found that FMD:PVP-K30:244FP achieved its best performance in terms of dissolution at the ratio of 1:1:1 when PVP-K30 and mesoporous silica Syloid 244FP (244FP) were chosen as combined carrier. SEM, DSC, and XRD studies indicated that furosemide existed in an amorphous form in the solid dispersion. FT-IR and molecular docking analysis showed that there might be an intermolecular interaction between FMD and the carrier. Moreover, the in vivo pharmacokinetics study revealed that the bioavailability of solid dispersion in rats had significant improvement. In particular, Cmax and AUClast were greatly increased by 2.69- and 2.08-fold in the solid dispersion (FMD-PVP-K30-244FP) group, respectively, and the relative bioavailability was 208.00%. In conclusion, the solid dispersion (FMD-PVP-K30-244FP) can significantly improve the solubility and oral bioavailability of furosemide. Mesoporous silica can be used as an excellent carrier material for furosemide, which can provide new ideas and methods for improving the stability of solid dispersion and further improving the dissolution of insoluble drugs. Graphical Abstract.

Effect of precipitation inhibitors on supersaturation and solubility of furosemide

Effect of precipitation inhibitors on supersaturation and solubility of furosemide

BCS Class IV Oral Drugs and Absorption Windows: Regional-Dependent Intestinal Permeability of Furosemide.

Biopharmaceutical classification system (BCS) class IV drugs (low-solubility low-permeability) are generally poor drug candidates, yet, ~5% of oral drugs on the market belong to this class. While solubility is often predictable, intestinal permeability is rather complicated and highly dependent on many biochemical/physiological parameters. In this work, we investigated the solubility/permeability of BCS class IV drug, furosemide, considering the complexity of the entire small intestine (SI). Furosemide solubility, physicochemical properties, and intestinal permeability were thoroughly investigated in-vitro and in-vivo throughout the SI. In addition, advanced in-silico simulations (GastroPlus®) were used to elucidate furosemide regional-dependent absorption pattern. Metoprolol was used as the low/high permeability class boundary. Furosemide was found to be a low-solubility compound. Log D of furosemide at the three pH values 6.5, 7.0, and 7.5 (representing the conditions throughout the SI) showed a downward trend. Similarly, segmental-dependent in-vivo intestinal permeability was revealed; as the intestinal region becomes progressively distal, and the pH gradually increases, the permeability of furosemide significantly decreased. The opposite trend was evident for metoprolol. Theoretical physicochemical analysis based on ionization, pKa, and partitioning predicted the same trend and confirmed the experimental results. Computational simulations clearly showed the effect of furosemide’s regional-dependent permeability on its absorption, as well as the critical role of the drug’s absorption window on the overall bioavailability. The data reveals the absorption window of furosemide in the proximal SI, allowing adequate absorption and consequent effect, despite its class IV characteristics. Nevertheless, this absorption window so early on in the SI rules out the suitability of controlled-release furosemide formulations, as confirmed by the in-silico results. The potential link between segmental-dependent intestinal permeability and adequate oral absorption of BCS Class IV drugs may aid to develop challenging drugs as successful oral products.

Physicochemical Studies on Interacting Some Cardiovascular Drug Pairs

Are increasingly seen to be important, some drugs, can undergo direct physical or chemical interaction with other drugs and render both drugs inactive. In the light of the above, this study aims to examine some pharmaceutical studies of physicochemical drug interactions including solubility and adsorption studies of selected cardiovascular drugs which are commonly involved in potential drug‐drug interaction (pDDIs) in the cardiovascular department in order to pave the path for preventing or at least reducing the incidence of pDDIs. To reach this objective, study encountered some practical consequences of the physical chemistry of drugs, especially their interactions with each other, or with various pharmaceutical adsorbents. The solubility of three cardiovascular drugs was tested in the presence of other drugs using the shake‐flask method. Those drugs were: aspirin, furosemide and amiodarone. Our results showed that spironolactone can affect the hydrolysis of aspirin if co‐administered at equivalent clinical doses, and therefore might reduce the efficacy of protective low‐dose aspirin. Moreover, the solubility of furosemide decreased in the presence of gentamicin. The solubility of amiodarone decreased in presence of warfarin, theophylline and lidocaine. In the adsorption experiments, aspirin and furosemide were selected as adsorbates. The adsorbents used were: activated charcoal, cholestyramine, kaolin, sodium hydroxide and sodium alginate. The experimental adsorption data were fitted to four isotherm models by both linear and non‐linear regression analyses. Freundlich isotherm provided the best fit for most adsorption data followed by Temkin and Langmuir isotherms. The highest adsorption capacity of activated charcoal and cholestyramine was for furosemide

Evaluation of Oleic Acid and Polyethylene Glycol Monomethyl Ether Conjugate (PEGylated Oleic Acid) as a Solubility Enhancer of Furosemide

Poor aqueous solubility limits the therapeutic efficacy of many marketed and investigational drugs. Synthesis of new drugs with improved solubility is challenging due to time constraint and expenses involved. Therefore, finding the solubility enhancers for existing drugs is an attractive and profitable strategy. In this study, PEGylated oleic acid (OA-mPEG5000), a conjugate of oleic acid and mPEG5000 was synthesized and evaluated as a solubilizer for furosemide. OA-mPEG5000 was evaluated as a nanocarrier for furosemide by formulating polymersomes. Solubility of furosemide in milli-Q water and aqueous OA-mPEG5000 solution was determined using shake flask method. At 37 °C, the solubility of furosemide in OA-mPEG5000 (1% w/w) and milli-Q water was 3404.7 ± 254.6 µg/mL and 1020.2 ± 40.9 µg/mL, respectively. Results showed there was a 3.34-fold increase in solubility of furosemide in OA-mPEG5000 compared to water at 37 °C. At 25 °C, there was a 3.31-fold increase in solubilization of furosemide in OA-mPEG5000 (1% w/w) (90.0 ± 1.45 µg/mL) compared to milli-Q water (27.2 ± 1.43 µg/mL). Size, polydispersity index and zeta potential of polymersomes ranged from 85–145.5 nm, 0.187–0.511 and −4.0–12.77 mV, respectively. In-vitro release study revealed a burst release (71%) within 1 h. Significant enhancement in solubility and formation of polymersomes suggested that OA-mPEG5000 could be a good solubilizer and nanocarrier for furosemide.

Formulation and development of fast dissolving oral film of a poorly soluble drug, frusemide with improved drug loading using mixed solvency concept and its evaluation

The aim of the present research work is to explore the application of mixed solvency concept to formulate and develop a fast dissolving oral film of furosemide with improved drug loading. In the present study, poorly soluble drug, furosemide was tried to be solubilized by employing the combination of physiologically compatible water-soluble additives (solubilizers) to formulate its fast dissolving formulations. For the development of fast dissolving oral film, firstly, different film forming polymers were tested for their film properties. The second fast dissolving layer was also formed and optimized. Solubility studies were conducted to select water-soluble additives for formulation of fast dissolving drug layer. Keeping the total concentration less than 40 % w/v of mixed blends, different aqueous blends were prepared employing solubilizers from among sodium benzoate, sodium acetate, sodium citrate, urea, niacinamide, glycerin, propylene glycol, polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600, and PVP K 30. Maximum solubility of furosemide was found in blends- F5 (10% sodium caprylate +2.5%sodium benzoate+ 2.5% niacinamide) and in blend F7 (10% sodium caprylate +2.5%sodium benzoate +2.5% sodium citrate + 2.5% niacinamide). Prepared films were evaluated for drug content, thickness, folding endurance, tensile strength and hydration ratio.
 Keywords: Furosemide, fast dissolving oral film, mixed solvency concept.

Preparation and characterization of furosemide nanosuspensions

Furosemide, a widely used loop diuretic, has a low aqueous solubility, and low permeability. Nanosuspensions have been widely used to increase the solubility of poorly soluble drugs. The aim of this study was to develop and characterize furosemide containing nanosuspensions. Furosemide nanosuspensions with Tween 80, were prepared using high pressure homogenization method using ultrasonic probe or ultra turrax, ball milling method, and combination of these methods. The physicochemical properties of furosemide, physical mixture and nanosuspensions were evaluated by FT-IR, DSC and X-ray analyses. Particle size, polydispersity index, zeta potential, solubility and permeability of nanosuspensions were also determined. FT-IR analysis revealed that characteristic peaks of furosemide were seen in all formulations. X-ray analysis indicated that crystalline structure of furosemide was preserved in nanosuspensions. The particle size of furosemide decreased significantly (p < 0.05) by using nanosuspension technology. Furosemide solubility was pH-dependent, and impact of nanosuspension on the solubility was more pronounced at lower pH values (e.g. pH 1.2). Furosemide permeability seemed to be influenced by nanosuspension preparation method. In conclusion, nanosuspension technology seems to be a promising approach for enhancement of solubility and permeability properties of poorly water soluble compounds, and it has an excellent potential to improve the bioavailability of such compounds.

Characterization of systems with amino-acids and oligosaccharides as modifiers of biopharmaceutical properties of furosemide

Furosemide is the most commonly prescribed diuretic drug in spite of its suboptimal biopharmaceutical properties. In this work, the addition of different amino-acids was studied with the aim of selecting an enhancer of the furosemide solubility. The best results were obtained with arginine. Also, binary (furosemide:arginine) and ternary (furosemide:arginine:β-cyclodextrin and furosemide:arginine:maltodextrin) systems were prepared by the kneading method and they were compared with their corresponding physical mixtures. These new systems were characterized by Fourier transform infrared and Raman spectroscopy, X-ray powder diffractometry, scanning electron microscopy, thermogravimetric analysis, and differential scanning calorimetry. In addition, dissolution studies were performed in simulated gastric fluid. The best results in relation to improving biopharmaceutical properties were obtained with a binary combination of furosemide and arginine, demonstrating that this system could result in a suitable candidate for the development of a promising pharmaceutical formulation of the drug.

Comparative evaluation of coprecipitation, solvent evaporation, and kneading as techniques to improve solubility and dissolution profiles of a BCS class IV drug

Purpose Furosemide bioavailability is limited by poor solubility and permeability. This study aimed to compare coprecipitation, kneading, and solvent evaporation as solubility and dissolution improvement techniques. Materials and methods Products were prepared with furosemide : polyvinylpyrrolidone : lactose at 1 : 1 : 2, 1 : 2 : 3, 1 : 3 : 4, 1 : 1 : 4, 1 : 2 : 6, 1 : 3 : 8 by coprecipitation, kneading, solvent evaporation or physical blending. They were characterized for physicochemical properties and interaction. Solubilities of furosemide from products were evaluated in water and n-octanol. Dissolution studies on the products were conducted in 0.1 N HCl using USP apparatus II. Results Solubility of pure furosemide was lowest in n-octanol (11.86 μg/ml) and highest in PBS (28.68 μg/ml). Infrared spectra revealed that characteristic peaks in pure furosemide were retained in its formulations, indicating chemical compatibility of furosemide and the excipients. Differential scanning calorimetry thermogram of furosemide showed a melting point at 220°C, which disappeared in its formulations − attributable to amorphization of the drug or overshadow by excipients. Furosemide significantly partitioned more (P kneading>physical mixtures>coprecipitation. Cumulative amount of furosemide dissolved from pure sample was 8%, whereas amounts from formulations were significantly higher (P Conclusion All the methods improved the solubilities and dissolution profiles of furosemide to various degrees; however, solvent evaporation method was the best.

Preformulation and physicochemical interaction study of furosemide with different solid lipids

The aim of the present work was to prepare and characterize the matrices of Furosemide (FRSM) with different solid lipids (Compritol 888 ATO, Hydrokote C, Imwitor 491, Imwitor 372P, and Witepsol H12) using Fourier transform infrared (FTIR), Raman, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy. The solubility of FRSM in various solid lipids followed the order of; Compritol 888 ATO > Witepsol H12 > Hydrokote C > Imwitor 491 > Imwitor 372. FTIR, Raman, DSC and XRD studies indicated no chemical interactions with Compritol 888 ATO, Imwitor 491 and Imwitor 372P. Scanning electron microscopic images of lipids, melted lipids, FRSM and FRSM-lipid matrices showed different morphological characteristics. In vitro drug release study showed the sustained release of drug from all lipid-matrices that followed Higuchi and Korsmeyer–Peppas model except FRSM-Hydrokote matrix. The best fit model of FRSM-Hydrokote matrix was zero order (R2 = 0.978). Conclusively, Compritol 888 ATO was selected as lipid of choice owing to maximum solubility, least chemical interaction and better sustained release profile.

A Systematic Approach to Design and Prepare Poly(meth)acrylate Based Solid Dispersions of Poorly Water-soluble Drug by Spray Drying

Objective of present study was to develop formulation which improves solubility of furosemide and stability of spray dried solid dispersion. Various processing parameters were optimized by applying DoE. In first step, screening of poly(meth)acrylates were carried out using solvent casting methods to select appropriate polymer. In second step, solid dispersion was prepared using optimized poly(meth)acrylate via spray drying process and trials were conducted as per DoE. Characterization of spray dried microparticles was carried out using SEM, DSC, XRD, in-vitro dissolution, and stability study. EUDRAGIT® E PO was screened as a suitable polymeric carrier in solvent casting method. In-vitro dissolution showed 100% releases within 20 min for spray dried powder as compared to 9% release for pure drug after 60 min in 0.1 N HCl. SEM analysis revealed conversion of crystalline shape to spherical shape. DSC and XRD confirmed that crystalline form was converted into amorphous form which was stable even after 3 months of storage. Outcome of DoE revealed that, feed rate has significant effect on %LOD while solid content has major effect on the process yield. So, present work indicates that EUDRAGIT® E PO formed a stable spray dried solid dispersion and it has ability to enhance dissolution of furosemide.

Inter-subject variability in intestinal drug solubility

Variability in oral drug absorption is a well-known phenomenon, but it is often overlooked for its potential effects in oral drug delivery. Understanding the mechanisms behind absorption variability is crucial to understanding and predicting drug pharmacokinetics. In this study, the solubility of furosemide and dipyridamole – drugs known to have highly variable oral bioavailabilities – was investigated in individual ileostomy fluids from 10 subjects with ulcerative colitis. For comparison, drug solubility was also determined in pooled upper gastrointestinal fluids from healthy human subjects and simulated intestinal fluids. Ileostomy fluid characterization revealed high variability in buffer capacity and to a lesser degree for pH. Drug solubility in ileostomy fluids showed high variability. Correlation analysis revealed that dipyridamole solubility in these fluids is pH-dependent, whereas furosemide solubility was highly correlated to buffer capacity and pH. The implications of these results might partly explain the high variability in bioavailability in vivo, assuming that most of the observed variability is due to the absorption, and not the elimination, process.

In vitro characterization and pharmacodynamic evaluation of furosemide loaded self nano emulsifying drug delivery systems (SNEDDS)

Poor water solubility is one of the reasons for erratic absorption after oral administration of furosemide (FSM), an antihypertensive loop diuretic. Self nano emulsifying drug delivery system (SNEDDS) is a novel drug delivery system utilized to improve the water solubility, permeability and ultimately bioavailability. FSM solubility was determined in various vehicles oils, surfactants and co surfactants. Self emulsification region for the rational design of SNEDDS formulations were identified by pseudoternary diagrams. Developed formulations were characterized by zeta potential determination, droplet size analysis, dilution test, viscosity determination, in vitro dissolution studies and in vivo pharmacodynamic evaluation. A remarkable increase in dissolution was observed for the optimized SNEDDS when compared with the plain FSM and marketed formulation by in vitro dissolution studies. The pharmacological effect of FSM was improved by SNEDDS formulation as compared to plain FSM. The study confirmed that the SNEDDS formulation can be used as a possible alternative to traditional oral formulations of FSM to improve its bioavailability.

Screening for physicochemical incompatibilities of intravenous drugs in intensive care units: the case of monobasic potassium phosphate and furosemide

ObjectivesPhysicochemical incompatibilities between intravenous drugs are a recurrent problem in hospital settings. Having observed a drug precipitation during Y-site administration in our intensive care units, we undertook an investigation to...

Mixed hydrotropy: Novel science of solubility enhancement

Conventional furosemide tablets are practically insoluble in water, have slow onset of action (45-60 min) and poor bioavailability (39-53%), and therefore cannot be given in emergency clinical situations like hypertension or pulmonary edema. So purpose of research was to provide a fast dissolving oral dosage form of furosemide, which can provide quick onset of action by using concept of mixed hydrotropy. Initially solubility of furosemide was determined individually in 4 hydrotropic agents namely urea, sodium acetate, sodium benzoate, sodium citrate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as solvent. Highest solubility was obtained in 40% sodium benzoate solution. Then different combinations of 2, 3 and 4 hydrotropic agents in different ratios were used to determine solubility, so that total concentration of hydrotropic agents was always 40%. Highest solubility was obtained in solution of urea+sodium benzoate+sodium citrate at optimum ratio of 15:20:5. This optimized combination was utilized in preparing solid dispersions by common solvent technique using distilled water as solvent. Solid dispersions were evaluated for flow properties, XRD, DSC, SEM and were also compressed to form tablets. Dissolution studies of conventional and prepared tablets were done using USP Type II apparatus. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing bioavailability of poorly water-soluble drugs by dissolving drug in nonionized form. The magical enhancement in solubility of furosemide is clear indication of its potential to be used in future for other poorly water-soluble drugs in which low bioavailability is major concern.

Aqueous solubilization of furosemide by supramolecular complexation with 4-sulphonic calix[n]arenes.

The solubilization of the practically water insoluble drug furosemide by guest:host inclusion complexation with 4-sulphonic calix[n]arenes has been reported. The 4-sulphonic calix[n]arenes are water-soluble phenolic cyclooligomers that form inclusion complexes with neutral molecules. The solubility of furosemide in acidic (pH < 4) aqueous solutions containing increasing concentrations of the calixarenes was determined at 30 degrees C and the concentration of furosemide in solution was determined by HPLC. Results showed that the molecular size of the 4-sulphonic calix[n]arenes and the concentration of the calix[n]arenes significantly influenced the increase in the solubility of furosemide. 4-Sulphonic calix[6]arene improved the solubility of furosemide the most (+/-104%) followed by 4-sulphonic calix[8]arene (+/-84-102%), while 4-sulphonic calix[4]arene increased the solubility of furosemide the least (+/-73-81%). The increase in furosemide solubility afforded by the calixarenes was most probably the result of the incorporation of the non-polar portions of the furosemide molecule into the non-polar cavities of the calixarenes similar to furosemide:cyclodextrin complexes. The driving force for this interaction was the reduction in the non-polar-water interfacial surface area when the furosemide (guest) molecules were inserted into the 4-sulphonic calix[n]arenes (host).

Enhanced in vitro permeation of furosemide loaded into thermally carbonized mesoporous silicon (TCPSi) microparticles

The combined release and permeation behavior of furosemide loaded into thermally carbonized mesoporous silicon (TCPSi) microparticles was studied in order to evaluate the potential of TCPSi-loading to improve permeation of furosemide, a BCS class IV compound. Permeation was studied across Caco-2 monolayers at pH 5.5, 6.8 and 7.4 from drug solutions and TCPSi particles. TCPSi-loaded furosemide (39% w/w) exhibited improved dissolution from the microparticles with greatly diminished pH dependence. At pH 5.5, where furosemide solubility restricted the amount that could be dissolved in the control solution to less than 30% of the dose contained in the TCPSi particles, the flux of TCPSi-loaded furosemide across Caco-2 monolayers was over fivefold compared to pre-dissolved furosemide. The improved permeation could be confirmed also from dose-corrected (% dose-permeated) results. At pH 6.8 and pH 7.4, where corresponding doses could be used in control solutions, more than fourfold permeability values were obtained with TCPSi-loaded furosemide. Effects on transepithelial electrical resistance (TEER) and mannitol permeability were monitored and suggest that monolayer integrity was not compromised by the drug-loaded TCPSi microparticles. The improved permeation observed from furosemide-loaded TCPSi particles suggests that the high local concentrations provided by the enhanced dissolution properties of TCPSi-loaded furosemide could prove beneficial for absorption.

Controlled release of furosemide from the ethylene-vinyl acetate matrix

The ethylene-vinyl acetate (EVA) matrix containing furosemide was prepared by the casting method and the release patterns were observed. The solubility of furosemide was determined as a function of volume fraction of polyethylene glycol 400. The release of drug from the matrix was studied as a function of temperature and drug concentration. Plasticizers such as the citrates and the phthalates were added for preparing the membrane to increase the flexibility of the EVA matrix. The solubility of furosemide was the highest when the concentration of PEG 400 was 40% (v/v). The release rate of drug from the EVA matrix increased with increasing temperature and drug loading doses. A linear relationship was found between the release rate and the square root of the loading dose. The activation energy ( E a), which was measured from the slope of the log P versus 1000/ T plots, was 12.33 kcal/mol for the 0.5% loading dose, and 11.58 kcal/mol for the 1.0% loading dose, and 11.00 kcal/mol for the 1.5% loading dose. Among the plasticizers used such as the citrates and the phthalates groups, diethyl phthalate showed the best enhancing effects in drug release. In conclusion, the application of an EVA matrix containing a plasticizer might be useful in the development of a controlled drug delivery system.

Formulation of an oral dosage form utilizing the properties of cubic liquid crystalline phases of glyceryl monooleate

Glyceryl monooleate is a Food and Drug Administration-approved food additive which has the ability to form various liquid crystalline phases in the presence of various amounts of water. The unique properties of the cubic liquid crystalline phase that result upon the presence of excess body fluids at body temperature were utilized to formulate an oral dosage form containing furosemide as the model drug. The aim was to develop a formula, which has both bioadhesive and sustained release properties of the resultant cubic phase, so that increasing gastric residence time to improve bioavailability of the drug and at the same time obtaining a sustained action. The system was found to be affected by the limited solubility of furosemide in both the carrier system and the pH of surrounding medium. As a consequence, the addition of some solubility modifiers was investigated in order to obtain the desired properties of the expected liquid crystalline system.