Claims:1. A pharmaceutical composition comprising Clobetasol loaded solid lipid nanoparticles (SLNs) and Nanostructured lipid carriers (NLCs) gel-based formulation against treatment of psoriasis.
2. The composition as claimed in claim 1, wherein the SLN were prepared SLNs prepared with 3% surfactant(Tween 80) concentration and 4 % lipid concentration (Compritol) and 10 mins HT to maintain small particle size.
3. The composition as claimed in claim 1, wherein the NLCs was prepared at 1:7.5 (Clobetasol to Compritol and Oleic acid) ratio and 10 min ST showed significantly lower particle size than other combinations, even lower than SLNs (prepared with only solid lipid). , Description:FIELD OF INVENTION
The present invention relates to a development of Clobetasol loaded SLNs and NLCs gel which had higher efficacy in psoriatic management.
BACKGROUND OF THE INVENTION
Psoriasis is a chronic papulosquamous skin condition that affects people of all ages and causes a significant burden on individuals and society. It's linked to a number of serious illnesses, including depression, psoriatic arthritis, and cardiometabolic syndrome. Chronic plaque psoriasis vulgaris, the most prevalent type, is caused by a combination of genetic predisposition (especially in the presence of the HLA-C*06:02 risk allele) and environmental triggers such streptococcal infection, stress, smoking, obesity, and alcohol use.
There are several phenotypes, with pustular and chronic plaque forms being distinguished by study. IL-17 and IL-23 have been identified as major drivers of psoriasis development in immunological and genetic investigations. Biological treatments that target these cytokines and TNF on the immune system have revolutionized the treatment of severe chronic plaque disease. Although psoriasis cannot be cured, it may be managed to reduce physical and psychological suffering by treating patients early in the disease process, detecting and avoiding related multimorbidity, establishing lifestyle changes, and using a customized therapy strategy.
The following prior art is being reported:
IN202141009486 The present invention relates to prepare nanostructured lipid carrier system for topical delivery of Clobetasol-loaded NLCs gel for ease of application on psoriatic dermal and to evaluate its anti-psoriatic efficacy compare with conventional Clobetasol ointment formulation. The objective was to develop a nanogel composed of clobetasol (CP)-loaded nanostructured lipid carrier (CP-NLC) and to evaluate its efficiency in imiquimod-induced psoriasis in mice. The ointment was formulated by simple melt dispersion whereas in this present invention Clobetasol loaded both Solid lipid nanoparticles and nanostructured lipid carriers were used for topical treatment of psoriasis and in this topical formulation gel was made.
IN202141009425 The present invention relates to topical application of the SLN gel showed reduction in psoriatic symptoms in IMQ induced psoriatic plaque model. Efficacy of SLN gel and ointment were compared the results like PASI scoring, histopathological study and ELISA showed that CP-SLNs gel have potential to treat psoriasis. To conclude SLNs gel was found to be more effective than ointment in treating psoriasis whereas in this present invention Solid lipid nanoparticles and nanostructured lipid carriers both were developed by using Clobetasol which formulated into topical based formulation for the treatment of psoriasis.

OBJECTS OF THE INVENTION
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows.
It is an object of the present disclosure to ameliorate one or more problems of the prior art or to at least provide a useful alternative
An object of the present disclosure is to provide Solid lipid nanoparticles and Nanostructured lipid carriers of Clobetasol.
Another object of the present disclosure is to provide Clobetasol loaded gel had higher efficacy in psoriatic management.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.

SUMMARY OF THE INVENTION
The following presents a simplified summary of the invention in order to provide a basic understanding of some aspects of the invention. This summary is not an extensive overview of the present invention. It is not intended to identify the key/critical elements of the invention or to delineate the scope of the invention. Its sole purpose is to present some concept of the invention in a simplified form as a prelude to a more detailed description of the invention presented later.

The present invention is generally directed to use of Clobetasol loaded Solid lipid nanoparticles and nanostructured lipid carriers topical formulation may have the pharmacological actions.
An embodiment of the present invention is for the conventional approach of SLN and NLCs which is associated to enhance drug permeation ability, good release profile and targeted drug delivery with excellent physical stability and low degradability etc.
Yet another embodiment of the invention is beneficial for high permeation ability in topical delivery of drugs and potentiate extended retention at the site of contagion.

BRIEF DESCRIPTION OF THE DRAWINGS
Fig 1: Formulation flow chart
Fig 2: Detailed treatment and time schema of the experiments.
Fig 3: Fish bone diagram: Cause-and-Effect Relationship between Material and Process attributes for designing of Lipid nanoparticles
Fig 4: Comparison spreadability profile for CP-ointment and CP-SLNs
Fig 5: Comparison spreadability profile for CP-ointment and CP-NLCs
Fig 6: In vitro drug release profile: CP-solution, CP-ointment, CP-SLNs gel and CP-SLNs gel in phosphate buffer (pH 5.5).

DETAILED DESCRIPTION OF THE INVENTION
The following description is of exemplary embodiments only and is not intended to limit the scope, applicability or configuration of the invention in any way. Rather, the following description provides a convenient illustration for implementing exemplary embodiments of the invention. Various changes to the described embodiments may be made in the function and arrangement of the elements described without departing from the scope of the invention.
EXAMPLES
Example 1 Preformulation Studies
In order to establish a suitable dosage from for a drug it was a pre-requisite to physicochemical properties of drug and other related properties too. Prior analysis is equally important in addition to drug development because the incompatibility between drug and excipients initial stages will further development the quality of dosage form and its therapeutic efficiency.
Example 2 Identification and Characterization
Organoleptic Evaluation
Clobetasol, a chosen drug was evaluated for odour, colour and texture.
Melting Point Range
The phase changes occur at a melting point of a chemical moiety was identified the temperature at which the equilibrium changes occur from solid to liquid. Melting point of the clobetasol propionate was estimated by using Thiel’s tube method. The melting range was recorded from first start to completely melt of sample.
Example 3 Construction of Calibration graph for CP
Protocol for stock solution
The wavelength at which maximum absorption of CP takes place was analyzed by dissolving a measured amount of drug in methanol. To construct standard graph 20 mg of CP was weigh accurately and transfer it to the 10 ml of methanol in a volumetric flask. 1 ml of stock was transferred into 100ml volumetric flask and make up the volume to 100 ml by using phosphate buffer of pH 5.5. From these serial dilutions were prepared in a concentration range of 2, 4, 6, 8, 10, 12, 14 μg/ml. Each sample was analyzed for λ max and standard plot were constructed between concentration vs absorbance. Finally, the method was validated and LOD was determined.
Example 4 Solubility Studies
Estimating the solubility of drug in various solvents aids in selection of lipids and other excipients for designing of LNP’s. Solubility was estimated by dropping amount of drug into a solvent and analyzed after attaining equilibrium. The solubility of clobetasol propionate was studied in various aqueous and non-aqueous solvents. Excess amounts of drugs were added to different solvents (10ml each) and agitated for 24 h using rotary shaker at room temperature. The solution was screened through filter paper (whatman filter paper No. 44) to obtain clear solutions, and the concentration of drug was estimated spectrophotometrically.
Example 5 Partition Coefficient
Partition coefficient (oil phase/ aqueous phase) is an estimate of drug hydrophobicity and it is a marker to predict the ability to cross biological membrane. Log P value greater than1 categorized as lipophilic, whereas less than 1 was an indicative for hydrophilic drug.
Po/w = (Coil/Caq) equilibrium
It could be approximated by measuring distribution coefficient of CP in n-octanol/water. Clobetasol Propionate (10mg) was added to 10mL each of n- octanol and distilled water in separating funnel. The mixture was stirred isothermally in a circular motion (so as to prevent emulsion formation) for 30 min until drug attains and kept aside for 1 h. The two phases were segregated and decanted separately. Analyze the drug concentration in organic phase and aqueous phase by measuring absorbance at λ max using UV.
Example 6 Initial Risk Assessment
Risk assessment is the primary concern of DoE based process and product development which comprises of finding interpreting and observing causes for risks were observed in the given formulation. In lipid nanoparticles (SLNs/ NLCs), the following failure modes are inadequate particle size, inadequate solubility, inadequate In-vitro drug release and kinetic instability. The observed risks were best evaluated by fish bone diagram (Ishikawa diagram) from figure no. 2.
Example 7 Preliminary screening for selection of lipids Solid and liquid) by saturation method
Screening of lipid blend (solid and lipid) was done to identify the lipids which enable maximum solubility of clobetasol. To execute the study 1000mg of lipid was taken in screw capped bottles and melt the mixture at melting temperature > 5°C of lipid. A geometric proportion of drug was added into each lipid with continuous stirring of 500rpm for 60min in vortex mixer. Stabilize the saturated mixtures for 24 hrs and smear the lipid mixture on whatman filter paper to determine the immiscibility between lipids. After the equilibrium solubility studies particulate characteristics were observed by DLS technique. In the end, mixture was subjected to centrifugation process using ultracentrifuge (Remi, Japan). 1ml of supernatant layer was taken into eppendorf tubes, diluted with ethanol and the drug concentration was analyzed by HPLC. Solubility analysis to extract drug experimented in triplicate and the results were represented as mean + SD (n=3) . Miscibility pattern and recrystallization was given in Table No 4.1
Table No 4.1: Equilibrium/ solubility studies saturation of Clobetasol in different liquid and solid lipids

Lipid type Examined lipids Solubility of 50% (w/w) Oleuropein in lipids Recrystallization after 24 hrs
Solid lipid Compritol 888 ATO Soluble No
Precirol Slightly soluble No
Tefose Slightly Soluble Yes
Stearic acid Slightly soluble No
Palmic acid Slightly soluble Yes
Liquid lipid Oleic acid Very soluble No
Labrafac Soluble No
Gelucire 53/13 Sparingly soluble No
Capmul Slightly soluble Yes
Capryol Very soluble No
Miglyol Sparingly soluble No

Example 8 Selection of lipid matrix ratio for lipid nanoparticles (SLNs/ NLCs)
The ratio of lipid matrix (solid lipid: liquid lipid) which offers maximum solubility for Clobetasol was observed by this method the ratios were chosen from 90:10, 80:20, 70:30, 60:40 and 50:50 (%w/w) solid lipid: liquid lipid melted lipids were blended for 30min at 1000rpm using vortex mixer. To 5ml of the blend, 50 ml of Tween 80 solution (1 % v/v) was added and homogenize blended mixture using High Speed Homogenizer at 8000rpm for 15min and reside the samples for 24hrs at RT and quality parameters characters were measured by Dynamic Light Scattering technique. Pre-Optimization processes for lipids were given in Table No 4.2 and Table No 4.3.
Example 9 Influence of phospholipid lipid matrix (w/w)/ (PL) ratio on lipid nanoparticles (SLNs/ NLCs)
Lipid matrix and PL were taken in ratios of 0.5:1, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 4:1 (%w/w) and homogenized using vortex mixer at 500rpm for 30mins. To this mixture 5ml of Tween 80 solution (0.5% v/v) was added and vortexed the sample using HSH at 10000 rpm for 10min. Set the samples aside for about 24hrs and particulate characters were measured using DLS technique .
Table No 4.2: Preliminary optimization process: Selection of solid lipid for SLNs
S.No Ingredients S1 S2 S3 S4 S5
Drug Clobetasol (mg) 50 50 50 50 50
Solid Lipid
1 Compritol ATO 888 (mg) 10
2 Precirol (mg) 10
3 Tefose (mg) 10
4 Stearic Acid(mg) 10
5 Palmic Acid (mg) 10
Acceptance Criteria: PS=10-400 nm; ZP = ±25 to ± 65 mV; PI=<0.6 (monodisperse), *Values were expressed as mean ± SD: n=3.Total Volume-100ml

Example 10 Selection of Drug to Solid & Liquid lipid Ratio for LNPs
The effect of concentration of drug on entrapment and loading of LNP’s were observed by selecting discrete ratios of drug and lipid blend. Melt the blend and mix the blend for about 30min at 500rpm using vortex mixer. Add 5ml of 0.5% v/v concentration of Tween 80 solution to melted lipid blend and vortex the samples using HSH at 8000rpm for 15min, kept the samples aside for 24hrs and particulate characters were measured by Dynamic Light Scattering technique. The mixtures were observed for and DL (%) and EE (%).
Table No 4.3: Screening method for Selection of Solid lipid & Liquid lipid
S.No Ingredients S6 S7 S8 S9 S10 S11
Drug Clobetasol(mg) 50 50 50 50 50 50
Liquid Lipid
1 Oleic Acid 2
2 Labrafac (mg) 2
3 Gelucire 53/13 (mg) 2
4 Capmul (mg) 2
5 Capryol (mg) 2
6 Miglyol 2
Solid Lipid Compritol ATO 888 (mg) 10 10 10 10 10 10
Surfactant Tween 80 (%) 1 1 1 1 1 1
Selection Criteria: PS=10-400 nm; ZP = ±25 to ± 65 mV; PI=<0.6 (monodisperse), *Values were expressed as mean ± SD: n=3. Total Volume-100ml

Example 11 Selection of Surfactant
Surfactant selection is important to design lipid nanoparticles (SLNs & NLCs). Surfactants such as Polaxomer 188, Tween 80, Plutrol F68, Cremophore RA 60 and span 80 chosen for screening and the influence of surfactant on particulate characters were measured by maintain the concentration of surfactant at constantly 1% w/v. Pre-Optimization process for lipids were given in Table No 4.4
Table No 4.4: Pre-Optimization process: Selection of surfactant for lipid nanoparticles (SLNs & NLCs)
Sl No. Ingredients S12 S13 S14 S15 S16
Drug Clobetasol (mg) 50 50 50 50 50
Selected lipid Compritol ATO 888 (mg) 10 10 10 10 10
Liquid Lipid Oleic acid 2 2 2 2 2

Surfactant
1 Plutrol F 68 2
2 Tween 80 2
3 Planticare 2
4 Span 80 (%) 2
5 Cremophore RH 60 2
Selection Criteria: PS=10-400 nm; ZP = ±25 to ± 65 mV; PI=<0.6 (monodisperse); *Values were expressed as mean ± SD: n= 3, Total Volume-100ml

Example 12 Optimization of formulation techniques to design lipid nanoparticles (SLNs/ NLCs)
Emulsification and homogenization method
Clobetasol loaded SLNs were formulated by emulsification-homogenization method and separated into two portions in which one portion was comprised of drug and lipid ratio (1:4), while the second portion comprised of an aqueous solution of stabilizer and surfactant. Drug and lipid blend was melted out 5ºC above the lipid melting point. Aqueous portion was heated to the exact similar temperature as like lipid phase. When both portions attain equilibrium, the aqueous phase was added into lipid phase in a drop wise manner and emulsified using HSH (IKA® T-10 basic Ultra-Turrax®, Germany) at 10,000 rpm for 15min. The resulted emulsion was subjected to ultrasonication using probe Sonicator (VibracellTM 700W; Sonics, USA) at 80% amplitude & duration of 5min. Cycles was repeated alternatively until it attains uniform particle size. The final formulation was subjected to cooling in an ice bath to form nanoparticle dispersion was formation with uniform PS.
Example 13 Emulsification and sonication method
Clobetasol loaded NLCs were formulated by emulsification and sonication method. Solid lipid (Compritol) and Liquid lipid (Oleic acid) were chosen in a ratio of 70:30 and melted above 5°C of their respective M.P. The ratio of drug: lipid ratio was 1:7.5 %w/w and measured amount of Clobetasol was dispersed in lipid matrix and homogenizes until it attains a clear solution. Pre heat the prepared aqueous surfactant solution to same temperature of lipid mixture and lipid blend was added a drop wise to a surfactant solution under continuous vortexing at 10000 rpm for 10 min to obtain primary emulsion followed by ultrasonication upto 10 min (30:5 on: off lych) to formulate NLC. Cooled the dispersion and analyzed he quality parameters of NLC. The % of aqueous phase was found to be 90% (by weight) and lipid phase was about 10% (by weight). Sodium azide (0.02%) was added to NLCs for the prevent of microbial growth.

Example 14 Solvent diffusion method
For this method 5mg of lipid blend was mixed with 5ml of organic solvent
(ethanol: acetone (1:1v/v) and heated in water bath at 40ºC. Dispense quickly into 20ml of surfactant solution at RT under mechanical stirring at 3000rpm for 30min until lipid nanoparticulate dispersion were resulted. Blank SLNs/ NLCs formulate by same procedure without drug. Desiccate the samples for 24hrs at RT to evaporate residual solvents, centrifuge the samples, collect the precipitate and redispersed it into 10ml of sodium dodecyl sulphate (0.3% w/v) to remove adsorbed free drug on surface of SLNs/ NLCs, characterize the samples for quality parameters.

Example 15 Spreadability of Clobetasol-loaded SLNs/ NLCs gel
Spreadability is an important physical property of topical gel which helps in uniform spreadability of drug on affected area. The spreadability of Clobetasol-loaded SLNs/ NLCs gel was characterized by parallel plate method. 0.5g of SLNs/ NLCs gel was placed at the center of the glass plate and another glass was laid above it. A weight of 5 to 200g was kept on a glass plate at an interval of 30s and the spreadability was circulated by measuring the diameter in two perpendicular directions. The following equation is used to estimate spreadability factor.
Sf=A/W
where Sf (cm2/g ) is the spreadability factor i.e., maximum spreaded area after total addition of weights. In fig. no. 4 and 5 plot was drawn by taking spreaded area on y-axis and weight on x-axis .
Example 16 In-vitro drug release studies of SLNs/ NLCs
In vitro release studies of CP loaded SLNs/ NLCs gel and plain CP suspension was analyzed out using modified Franz diffusion cell containing a receptor volume of 15 ml using cellulose acetate membrane (MWCO- 12000–14000 Da, pore size- 2.4nm (HIMEDIA, Mumbai, India) and phosphate buffer pH 5.5 as dissolution medium. Surface area of membrane was 1.95cm2 was pre-soaked in double-distilled water for 12hrs, and this membrane was mounted on placed on the Franz diffusion cell filled with phosphate buffer (pH5.5). Agitate the sample in receptor compartment using magnetic stirrer at 350rpm and whole assembly was kept at temperature of 37.0 ± 0.5ºC. The samples containing 2mg drug (plain drug suspension and CP loaded SLNs/ NLCs dispersion) was spreaded homogeneously on the membrane of donor compartment and stirred well. Sampling was pipetted out through from the receptor compartment at a predetermined time intervals of 0, 6, 8, 10, 12 and 24hrs and equal volumes of fresh a dissolution medium was replaced immediately. Analyze the sample by using HPLC at 239nm and graph was plotted between time and percent drug release. Studies were done in triplicate for each sample.

Example 17 In-vitro Release Kinetic Studies
The drug release pattern was subjected to release kinetics in order to predict the release mechanism and its order of kinetics from Clobetasol loaded lipid nanoparticles (SLNs & NLCs). The first 80% of drug release profile were fitted into zero, first order and the multiple regressions (R2) were compared. The selected data was fitted into Higuchi to determine the drug release by diffusion or dissolution. From the data and fig no.6 , ‘n’ values were observed and if n= < 0.5, drug release follows Fickian diffusion, if n=1-Non-Fickian diffusion and if n>1.0- Non-Fickian Supercase II transport.

Example 18 Ex Vivo Skin Permeation Studies
In vitro skin distribution studies was done quantity the distribution of Clobetasol permeated through plain CP suspension, CP loaded SLNs suspension, CP-ointment, CP-SLNs gel and CP-NLCs gel using sheep skin. The skin distribution studies were executed using Franz diffusion cells. Skin samples were treated with various formulations (plain CP suspension, CP loaded SLNs suspension, CP-ointment, CP-SLNs gel and CP-NLCs gel) containing drug in an amount of equivalent 300mg (6hrs for each test sample). At the end of the study, the skin samples were washed and refrain from the Franz cells. Epidermal and dermal layers were desectioned using tweezers. Homogenize the skin layer with 5 ml methanol to extract the drug and analyze the sample for CP concentration using UV spectroscopy at 239 nm.
Example 19 Confocal laser scanning microscopy (CLSM)
For CLSM studies, SLNs and NLCs were formulated as disused above without drug.Coumarin-6 was added at a concentration of 0.15µmol/mL and dialyzing bags were used to remove unentrapped coumarin-6. Mice skin was fixed on the glass slide and formulation was applied on skin surface. In the presence of fluorescence was observed in skin layers by employing confocal laser scanning microscope (Olympus FV10i, M/s Olympus Singapore Pte Ltd., Singapore).
Example 20 Histological evaluation
After permeation experiments, porcine skin was subjected to histopathological studies. Skin was processed by rinsing and washing with normal saline followed by fixation using 10% neutral formalin buffer solution. The samples were processed in automatic tissue processor with isopropanol and embedded with paraffin, sectioned using microtone of 5μm size. Stain the tissues using hematoxyline and eosin observed the sample at 400x magnification using electron microscope.
Example 21 Anti-psoriatic efficacy studies of Lipid nanoparticles (SLNs/ NLCs) in BALB/C Mice
In Vivo Imiquimod-Induced Psoriatic Plaque Model
BALB/c mice were used to develop imiquimod induced psoriatic plaque model. Mice of 8-11 weeks and weight of 15-20 g was selected and housed under temperature conditions 23 ± 1°C, humidity55 ± 5 % and 12 hrs light/dark cycles with food and water ad libitum. Animals were grouped as follows Group-I (normal /sham), Group-II (negative control), Group-III (positive control), Group-IV (CP-Ointment) and Group-V (CP-SLNs/ NLCs) Table No 4.5.
Animals were depilated on dorsal side prior taking into study and 62.5mg of Imiquimod cream was applied on dorsal skin and right ear for six consecutive days except normal/sham group received vaseline, positive control was treated with 100mg/day of betamethasone valerate ointment, while group IV received CP-ointment (0.05mg/d) and group V received CP-loaded SLNs (0.05mg/d). Above mentioned same protocol follows to CP loaded NLCs formulation. These are the parameters were observed during study in mice change in body weight, psoriasis scoring area index (PASI) like erythema, scaling, skin thickness and both ears were measured by screw gauge assessed for all groups at 0, 2, 4, 6th day during treatment. Animals were scarified on 7th day by cervical dislocation, skin samples collected from mice and washed with buffer fixed with 10%v/v formalin solution to examine the pathological changes in the tissues and kept at -800C for to determine cytokine levels at the same spleen weight of all the animals recorded Figure No 4.2.
Table No 4.5: Treatment protocol and efficacy studies in IMQ induced Psoriasis in CP-loaded SLNs/ NLCs gel.
Animals Group Days
0 1 2 3 4 5 6
Group-I Sham -- -- -- -- -- -- --
Group-II
Negative control -- IMQ IMQ IMQ IMQ IMQ IMQ
Group-III
Positive control -- IMQ IMQ IMQ+
BMVb IMQ
BMV IMQ+
BMV IMQ+
BMV
Group-IV
CP ointment -- IMQ IMQ IMQ+
CP ointment IMQ+
CP ointment IMQ+
CP ointment IMQ+
CP ointment
Group-V
CP-SLNs/ NLCs -- IMQ IMQ IMQ
CP-SLNs/ NLCs IMQ
CP-SLNs/ NLCs IMQ
CP-SLNs/
NLCs IMQ
CP-SLNs/
NLCs
IMQ- Imiquimod, BMV- Betamethasone valerate

Example 22 PASI scoring of Psoriasis
The Severity of inflammation in the dorsal region of the skin mice was observed through PASI Scoring. Inflammatory markers include scaling, thickness of epidermis, erythema and scoring was observed on 0, 2, 4 and 6 day treatment days. Scoring was given in a scale of numbers from 0 to 4 based on severity of erythema, skin thickness and scaling i.e score 0 (none), score 1 (slight), score 2 (moderate), score 3 (severe), and score 4 (very severe).
Example 23 Changes of Spleen in Mice
The spleen was isolated from mice and weighed it. Splenomegaly was measured by observing the change in ratio of spleen to body weight.
Example 24 Enzyme Linked Immunosorbent Assay (ELISA)
The levels of inflammatory mediator’s i.e., IL-17, IL-22, IL-23, and TNF- α levels were determined using ELISA. At the end of the psoriatic study, skin samples were stored at -80°C until further analysis. Homogenize the tissue samples with buffer (10 mM Tris pH 7.4, 150 mM NaCl, 1% TritonTM X-100) using tissue homogenizer at 4000rpm for 10min. followed by centrifuge the mixture at 10000 rpm for 15 min using cooling centrifuge at 4°C and levels of cytokines were quantified using quantitative mouse ELISA kits (R&D Systems, Minneapolis, MN) as per specified manufacturer protocol.
While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation