AN ANALYTICAL AND EXPERIMENTAL RESEARCH FOR FORMULATION OF SELF EMULSIFYING DRUG DELIVERY SYSTEM
Yogendra Kumar Dube
M. Pharm Student, Bhabha Pharmacy Research Institute Prof. Rishikesh Sharma
Bhabha Pharmacy Research Institute 1. BIOAVAILABILITY
(Brahmankar, D. M., & Jaiswal, S. B.
2009)
Bioavailability is an critical standards of dosage form. In line with food and Drug management guiding principle, bio availability is defined because the rate and quantity to which an lively element is absorbed from a drug product and will become to be had on the website of motion. For drug products that aren't intended to be absorbed into the blood circulation, bioavailability can be assessed by using measuring the supposed mirror and the charge and volume to which the energetic ingredient or energetic moiety will become available at the site of action
According to global health organisation hints, Bioavailability is described as: the rate and volume to which an active drug component or healing moiety is absorbed from a drug product and turns into to be had on the site of drug action (WHO, 1986).
1.1 Biopharmaceutical Classification System (BCS)
(FDA, 2000; Amidon et al., 1995)
Biopharmaceutical classification system (BCS) is a scientific framework for classifying a drug substance based on its aqueous solubility and intestinal permeability. Biopharmaceutical classification system takes into account three major factors: solubility, intestinal permeability, and dissolution rate, all of which govern the rate and extent of oral drug absorption from immediate release (IR) solid oral-dosage forms).
Class Solubility Permeability
Class 1 High High
Class 2 Low High
Class 3 High Low
Class 4 Low Low
Table 1.1 Biopharmaceutical classification systems
2. LITERATURE REVIEW
Bachynsky, M. O. et al. (1997): reported dosage forms having self-emulsifying system shows promising approach to improve in vitro rate of dissolution of lipophilic compounds and also its oral absorption. In this system, a surfactant and/or a co-surfactant of medium chain glycerides, is to be added to a oil dissolving poorly soluble drug. In this present study, surfactants with different HLB surfactants with different oils compositions were being evaluated for their self-emulsifying performances, results proved that surfactant HLB and fatty acid chain length have a significant effect on self-emulsifying system; 10-15 HLB of a surfactant and C8-C10 medium chain glyceride were the most effective.
Even the critical surfactant concentration and fatty acid glycerides concentration were optimized for self-emulsifying system.
Odeberg, J. M. et al. (2003) tried to enhance bioavailability of lipophilic carotenoid astaxanthinhaving antioxidant activity. In this study, healthy male volunteers received 40mg astaxanthin, as food then analysed for plasma concentrations. Pharmacokinetic parameters were being calculated and rate and extent absorption can get. From 3 developed lipid based formulations: all 3 showed enhancement in bioavailability with reference. The highest oral bioavailability was found formulation having a high polysorbate 80.
Odeberg, J. M. et. al (2003) found the general promising characteristics of SEDDS for oral administration of lipophilic drug using natural lipid acting as surfactant like Galactolipids, polar lipids present in chloroplast of green plants and partly the human diet. 3 clinical studies: screening study, prediction study and confirmatory study;
17 formulations were being studied in healthy volunteers. Lipophilic peptide cyclosporine was included in SEDDS for administration and pharmacokinetic
parameters were estimated, which showed rate and the extent of absorption. It found that oat oil and medium chain glycerides increased absorption like Sandimmun Neoral®, cyclosporine commercial dosage.
3 SCOPE OF RESEARCH WORK
Improves solubility and dissolution of drug.
Improves balance of drug and method.
Increases drug absorption through lymphatic machine.
Decreases first bypass metabolism.
Improves in vivo bioavailability of drug.
Decreases side effects of drug.
Solidification of liquid SE gadget improves its bodily & chemical stability.
Improves therapeutic performance &
effectiveness of drug.
Set alternative to conventional oral method.
Increases affected person compliance.
Benefited to patients, industry and scientists and so forth.
4 PREFORMULATION STUDY
(Lachman, L. and Lieberman, H. A., 1990) (Howard Y. A. and Galen, W.R. 2000) (Jain, N.K. 2006) (Gibson, M. 2009) (Furniss, B. S. & vogel A. I., 1978)
Preformulation research are of amazing significance for development of excessive nice dosage formulations inside the quick period. On this, physical &
chemical characteristics and derived homes of API are decided and evaluated correctly. This is the primary studying section earlier than components development. Via this study, we are able to decrease errors, reduce the costing, and reduce no of trials. Preformulation research like fundamental characterization research (Organoleptic homes, melting point, solubility, and pH) and spectroscopic studies (UV and IR) had been accomplished on Atorvastatin drug samples.
4.1 Methodology for Liquid Smedds 4.1.1 Screening of Components a) Solubility study
(Patel, J. et al. 2011) (Jha, S. K. et al.
2011) (Reddy, M. S. et al. 2011)
Selection of various additives for the system of SEDDS specifically relies upon on one standards i.E. Solubility of poorly
water soluble drug in oils, surfactant and co-surfactants. The reason behind concerning about solubility of drug in oil is due to the fact the capability of SEDDS to maintain the drug in solubilized shape is substantially laid low with the solubility of drug in oils. For willpower of solubility in diverse oils, surfactant & co-surfactant is performed by means of including an extra amount of drug in 2mL of selected oils (Oleic acid, Soyabean oil, captex 355 etc.), surfactant (Tween eighty, Labrafil M1944 CS, Span 80 and so on.) in 5mL potential vials. The mixture had been then saved for seventy two hours at room temperature to reach equilibrium. Then the equilibrated samples were centrifuged for 15 min at 3000rpm. Supernatant changed into taken and filtered via 0.45 µm membrane filter. The amount of Atorvstatin dissolved was found the use of UV spectrophotometer at 246 nm.
Table.4.1 Different Oils, Surfactants &
Co-surfactants used in solubility study 4.2 Formulation of Solid Smedds of Atorvastatin
(Mahapatra, A. K., & Murthy, P. N. 2014) Strong SMEDDS of Atorvastatin have been organized the use of adsorption method. The selected liquid SMEDDS of Atorvastatin was adsorbed onto MCC, Magnesium oxide, Aerosil 200 service one at a time by way of physical blending in a mortar and pestle and were checked for loading efficiency at the service. The strong SMEDDS mass became combined to make sure uniform distribution after which mass was surpassed through sieve and dried and saved until use. Stable SMEDDS of equal dose of Atorvastatin were being stuffed in HGC length.
0.1 0.89 99.01 0.1 0.15 0.84 99.01 3.25 4.33 5.28 90.39 5.54 5.76 7.91 86.33 7.93 7.94 11.88 80.18 9.48
Table 4.2 Formulation of solid SMEDDS
4.3 Characterization of Solid Smedds of Atorvastatin
Micromeritics Properties- The Organoleptic properties of Solid SMEDDS like colour and physical appearance were checked visually and Micromeritics properties like Angle of repose, BD, TD, % C.I. & H.R. were evaluated and tabulated.
Drug Content- It was predicted by API extracting (Atorvastatin) from Solid SMEDDS and analyzed spectro photometrically. (Patel P. A., et al., 2010).
Solid SMEDDS comparable to 20 mg Simvastatin weighed accurately and dissolved in 10 ml methanol & diluted with double distilled water. Solution was filtered through 0.45 µm and after dilution, analyzed UV-Vis spectrometric ally at λ max.
%Transmittance- Stability of micro emulsion of solid SMEDDS was measured using % T at different dilutions. All Solid SMEDDS (equivalent to drug dose) were accurately weighed and diluted to 100 ml with water. Flask was inverted to get proper emulsification. Resultant fine emulsion was kept at rest for settlement of solid content and emulsion checked for relative turbidity measurements & T was taken in UV spectrophotometer taking distilled water as blank. For each sample three replicates were performed.
5. PREFORMULATION STUDY
(Lachman, L. and Lieberman, H. A., 1990) (Howard Y. A. and Galen, W.R. 2000) (Jain, N.K. 2006) (Gibson, M. 2009) (Furniss, B. S. & Vogel A. I., 1978)
5.1. Characterization of Atorvastatin Calcium
The characterization of natural Atorvastatin calcium became carried by way of acting exams like Organoleptic houses, melting factor determination, solubility evaluation, pH, loss on drying, and so on. (Rajkondwar, V. V. et al. 2009) (Desai, S. A. et al. 2015).
Table 5.1 Characterization of Atorvastatin Calcium Characters Specification Observations Appearance White to off
white crystalline powder
white,crystalline powder with characteristic odour Melting
range 160 °C 159-161°C
Solubility 0.0004 mg/ml water insoluble and sparingly soluble in ethanol, methanol &
acetonitrile.
Water insoluble 0.33 µg/ml; but
soluble in
methanol,
ethanol(11mg/ml), chloro form,DMSO and acetonitrile.
Loss on
drying Should not be >
than 0.3% 0.22%
5.2 Spectroscopic Study for Atorvastatin
UV Spectroscopy of Atorvastatin
Here, λ max of Atorvastatin in all solvent systems are shown.
Solvent media Λ max (nm)
Methanol 246
pH 1.2 246
Table 5.2 Maximum absorption (λ max) of Atorvastatin in different mediums
Fig. 5.1 Atorvastatin UV absorption maxima in Methanol
From the scanning of Atorvastatin in different solvent mediums from 200-400 nm in UV spectra, it was found that Maximum absorption (λ max) of Atorvastatin in different medium was 246 nm. Calibration curve of Atorvastatin in methanol, pH 1.2, pH 7.0 phosphate buffer with 0.5% SLS has been shown.
Absorbance = 0.041 * concentration + 0.030
Correlation coefficient = 0.997
Table 5.3 Calibration Curve of Atorvastatin
S. No Conc.(ug/ml) Abs.
1 2 0.221
2 4 0.413
3 6 0.611
4 8 0.845
5 10 0.939
Fig. 5.2 Calibration curve of Atorvastatin in Methanol 5.3 IR spectroscopy of Atorvastatin The characteristic absorption peaks of Atorvastatin in FTIR spectrum of Atorvastatin are shown.
Fig. 5.3 FTIR of Atorvastatin
From the Atorvastatin FTIR spectrum compared with standard, It was found that sample of Atorvastatin was identified as a pure compound.
5.4 Determination of Saturation Solubility Of Drugs In Vehicles
(Patel, J. et al. 2011) (Jha, S. K. et al.
2011) (Jha, S. K. et al. 2011) (Reddy, M.
S. et al. 2011)
5.4.1 Determination of the saturation solubility of Atorvastatin in Vehicles and screening of vehicles
Various oil, surfactant & co-surfactant were screened by solubility of Atorvastatin in different vehicles as per the solubility method described, solubility of Atorvastatin in different vehicles were determined using UV method and using calibration curve in methanol.
Table 5.4 Saturation Solubility of Atorvastatin in different vehicle
Vehicle Solubility(mg/ml) Average
solubility (mg/ml)
*Average solubility mean ± S.D (mg/ml)
I II III
Oils Oleic acid 46 41 38 41.6666667 41.667±4.041
Soyabean oil 32 27.5 28 29.1666667 29.167±2.466
Sunflower oil 41 37 44 40.6666667 40.667±3.512
Olive Oil 19 19 21 19.6666667 19.667±1.155
Captex 355 45 48 49 47.3333333 47.333±2.082
Surfactant Tween 80 60 61 61 60.6666667 60.667±0.577
Labrafil M2125CS 39 38.5 40 39.1666667 39.167±0.764
Span 20 60 55 58 57.6666667 57.667±2.517
Tween 20 55 56 59 56.6666667 56.667±2.082
Span 80 53 58 60 57 57±3.606
Co-Surfacatnts Propylene glycol 11 12 14 12.3333333 12.333±1.528
PEG 400 65 68 69 67.3333333 67.333±2.082
*Standard
Deviation (n=3)
Table 5.5 Solvent showing best solubility for Atorvastatin
Vehicle Solubility(mg/ml) Average
solubility(mg/ml) I
Oil 45 47.33
Surfactan 59 64.33
67 64
Fig. 5.4 Saturation solubility of Atorvastatin in Different Vehicles As per solubility data of
Atorvastatin in different oils, maximum amount of Atorvastatin dissolved in Oleic Acid. It was selected as oil having Atorvastatin solubility of 47.333±2.081 mg/ml for ternary phase diagram.
As per solubility data of Atorvastatin in different surfactants, maximum amount of Atorvastatin dissolved in Tween 80. So, Tween 80 was screened as surfactant having Atorvastatin solubility of 64±3 mg/ml for ternary phase diagram respectively.
As per solubility data of Atorvastatin in different co-surfactants, maximum amount of Atorvastatin dissolved in PEG 400. So it was selected as co-surfactant having atorvastatin
solubility of 64.333±4.726 mg/ml for ternary phase diagram.
5.5 Construction of Ternary Phase Diagrams For Different Systems
(Patel, J. et al. 2011) (Jha, S. K. et al.
2011) (Jha, S. K. et al. 2011) (Reddy, M.
S.et al. 2011)
For optimization of excipient concentration for Atorvastatin SMEDDS, Atorvastatin SMEDDS and Rosuvastatin SMEDDS formulations, ternary diagrams generated by water titration technique using chemix or Sigma plot 11.0 software
& from it, highest micro-emulsion zone (region) were found out to select optimum excipient concentration
O= Oil S=Surfactant
Vehicle Solubility(mg/ml) Average
solubility (mg/ml)
*Average solubility mean
± S.D (mg/ml)
I II III
Oil Oleic Acid 45 48 49 47.3333333 47.333±2.082
Surfactant Tween 80 67 61 64 64 64±3
Co-Surfactant PEG 400 59 68 66 64.3333333 64.333±4.726
Sm ix O +S m ix O E W O E W O E W O E W O E W 5 + 95 0.0 5 0.9 4 99 .01 0.0 5 0.9 4 99 .01 0.0 5 0.9 4 99 .01 0.0 5 0.9 4 99 .01 0.0 5 0.9 4 99 .01 10 +9 0 0.1 0.8 9 99 .01 0.1 0.9 99 0.1 6.9 93 0.1 0.8 9 99 .01 0.1 0.8 9 99 .01 15 +8 5 0.1 5 0.8 4 99 .01 3.2 5 3.7 4 93 .01 4.4 9 9.4 8 86 .03 1.1 1.2 6 97 .64 0.1 5 0.8 9 98 .96 20 +8 0 4.3 3 5.2 8 90 .39 5.5 4 6.7 9 87 .67 6.9 8 11 .89 81 .13 4.2 9 5.1 8 90 .53 0.1 6 0.9 2 98 .92 25 +7 5 5.7 6 7.9 1 86 .33 7.9 3 10 .67 81 .4 13 .49 12 .18 74 .33 5.6 7 7.7 8 86 .55 0.2 4 0.8 8 98 .88 30 +7 0 7.9 4 11 .88 80 .18 9.4 8 12 .38 78 .14 14 .94 21 .99 63 .07 7.8 4 10 .22 81 .94 0.3 0.7 99 40 +6 0 17 .77 27 .6 54 .63 19 .85 28 .73 51 .42 22 .99 30 .12 46 .89 17 .42 26 .63 55 .95 4.6 7 6.2 2 89 .11 50 +5 0 37 .5 27 .9 34 .6 36 .55 34 .97 28 .48 38 .84 40 .54 20 .62 36 .99 26 .32 36 .69 6.7 6.4 4 86 .86 60 +4 0 47 .22 32 .27 20 .51 48 .9 33 .2 17 .9 52 .95 33 .88 13 .17 46 .6 32 .2 21 .2 23 .4 19 .11 57 .49 70 +3 0 52 .15 28 .77 19 .08 60 .36 27 .23 12 .41 65 .11 24 .34 10 .55 50 .85 29 .08 20 .07 47 .66 20 .09 32 .25 80 +2 0 71 .73 19 .38 8.8 9 72 .62 18 .18 9.2 76 .14 15 .09 8.7 7 72 .33 18 .85 8.8 2 62 .44 17 .54 20 .02 90 +1 0 81 .81 9.0 9 9.1 82 .6 9.0 9 8.3 1 82 .97 9.3 8 7.6 5 81 .81 9.0 9 9.1 81 .82 9.0 9 9.0 9
(1: 2) (% ) (1: 3) (% ) (1 :1 ) ( % ) (2 :1 ) ( % ) (3 :1 ) ( % )
Cos= Co- surfactant Smix = S/Cos
ATV = Atorvastatin
PD No.= phase diagram no.
PD
No. Drug Oil Surfactant Co-
surfactant Smix 1 ATV Oleic
Acid Tween 80 PEG 400 1:1 2 ATV Oleic
Acid Tween 80 PEG 400 1:2 3 ATV Oleic
Acid Tween 80 PEG 400 1:3 4 ATV Oleic
Acid Tween 80 PEG 400 2:1 5 ATV Oleic
Acid Tween 80 PEG 400 3:1
Table 5.6 List of phase diagrams for different ratios of S mix
Table 5.7 Different ratio of Smix and Oil
5.6 Ternary Phase Diagram of Atorvastatin Smedds
Smix = S/C O= Oil (Oleic Acid) S = Surfactant (Tween 80) C = Co-surfactant (PEG 400) W= Water
Fig. 5.5 Phase Diagram No.1
Fig.5.6 Phase Diagram No. 2
Fig. 5.7 Phase Diagram No. 3
Fig. 5.8 Phase Diagram No. 4
Fig. 5.9 Phase Diagram No. 5 5.7 Formulation of Liquid SMEDDS
Formulation of SMEDDS of Atorvastatin
Based on the area of high micro emulsion region from the phase diagrams, Atorvastatin SMEDDS formulations A1 to A5 were successfully prepared without turbidity or phase separation using oil Oleic acid, surfactant Tween 80 and co- surfactant PEG 400 with Smix ratio of 1:1. The weight of the formulation was kept approximately 500 mg. Amount of Atorvastatin in all the formulation was kept constant (20 mg).
Table 5.8 Formulation Batches of liquid SMEDDS of Atorvastatin 5.8 Evaluation/Characterization of
Liquid SMEDDS
The evaluation tests were performed for selected formulations of SMEDDS of Atorvastatin (A1 to A5)
5.8.1 Macroscopic Evaluation by Visual Assessment and Robustness to Dilution With pH Effect
Macroscopic assessment like self- emulsification efficiency, look in phrases of colour, transparency, phase separation and precipitation of API changed into achieved visually without delay after dilution and after 24 hrs for all decided on SMEDDS even after dilutions.
A1 A2 A3 A4 A5
Colour Uniform
slight blue Uniform Uniform
Less uniform Less uniform Transparenc
y Uniform Uniform Less
uniform Less uniform Less uniform
Phase NO NO Very Clear Clear
separation Slight separation separation
Precipitation Clear,
stable Clear,
stable Clear,
stable Turbid,
Unstable Turbid, unstable Table 5.9 Macroscopic Evaluation of Atorvastatin SEDDS Formulations A4 and A5 were turbid and
unstable emulsions and even showed phase separation and precipitations. So they were not taken for dilution and pH
effect study. Formulations A1, A2 and A3 were clear, good & stable without any sign of precipitation even after 24 hrs of dilution.
Table 5.10 Effect of dilution on Atorvastatin Liquid SEDDS SMEDDS A2 were affected by dilution
with any mediums (distilled water or pH 1.2 or pH 7.0 medium). A1 & A3 of Atorvastatin were robust to dilution with all mediums without precipitation and
phase separation. Even there was no significant effect of pH found on any SMEDDS, because non-ionic surfactants have very very less effects of pH.
Phase separation and precipitation
Dilution Effect of pH
10 times
100 times
1000 times
Water pH 1.2
pH 7.0 buffer
A1 No No No No No No
A2 No No Yes No No No
A3 No No No No No No
A1 A2 A3 A4 A5
OIL %+ SMIX % 20+80 25+75 30+70 35+65 40+60
Drug 20 20 20 20 20
Oil 96 120 144 168 192
S mix (1:1) 384 360 336 312 288
Surfactant 192 180 168 156 144
Co surfactant 192 180 168 156 144
Total 500 500 500 500 500
5.8.2 % Transmittance Test
Formulation *% Transmittance ± S.D Distilled water 0.1 N HCl
A1 88.82±0.08 88.86±0.015
A2 99.42±0.008 99.45±0.05
A3 77.76±0.098 78.10±0.004
A4 44.27±1.38 40.79± 2.365
A5 32.13 ± 1.16 35.89 ± 1.72
Table 5.11 % Transmittance From the above table, it was seen that
formulations A4, A5 were milky white and unclear showing very less % Transmittance values which are unacceptable and hence they were not undergone to further characterisation studies. Formulations A3 shows very less
% transmittance, so they are somewhat unclear. A1 and A2 shows % Transmittance near to 100% so they are very clear & transparent & does not affected when diluted with SGF.
5.8.3 Viscosity Determination
This SMEDDS is usually administered in SGC/HGC. So, it must not be too thick but should be pourable.
Formulation
Viscosity (cps)
Viscosity of 10 times diluted
(cps)
A1 218 21.40
A2 212 20.4
A3 225 23.32
Table 5.12 Viscosity of liquid SMEDDS formulations of Atorvastatin
Viscosity of all SMEDDS formulations without dilution were found to be in range of 180 cps to 225 cps, means that formulation possess Newtonian type flow so there is no problem infilling of formulations in hard gelatin capsule and even that is without risk of leak. As SMEDDS formulations were diluted 10 times with water, microemulsion viscosity was decreased, it means that on oral administration of SMEDDS, it is diluted with stomach fluid and so viscosity decreases and facilitates absorption from the stomach.
5.8.4 Thermodynamic Stability Study Thermodynamic stability studies were being done to judge and discard metastable system within short period.
Actually macro emulsions face the problems of phase separation due to
instable kinetics behaviour, while micro emulsions are thermodynamically stable systems without phase separation problems. So if formulations pass thermodynamic studies, it means that they are not metastable systems and they will form micro emulsions probably.
Formu lation
Heating- cooling cycle
Centrifugatio n
Freeze thaw cycle
A1 Passes Passes Passes
A2 Passes Passes Passes
A3 Passes Passes Passes
Table 5.13 Thermodynamic stability study of formulations of Atorvastatin Physical stability of SMEDDS influences its method performance. Poor balance of SMEDDS leads to segment-separation. So thermodynamic stability research had been executed. Here in all decided on liquid SMEDDS formulations passed heating cooling test, then they exposed centrifugation, in which no sign of phase separation was visible. Then after freeze thaw cycle take a look at, formulations showed no sign of section separation, creaming and cracking. This means that all decided on SMEDDS formulations had been thermodynamically stable.
From results, it was found that all formulations of selected liquid SMEDDS of Atorvastatin (A1, A2 & A3) passed preliminary thermodynamic stability studies.
5.9 Formulation of Solid SMEDDS of Atorvastatin
Solid SMEDDS of Atorvastatin from selected liquid SMEDDS were successfully developed using adsorption technique onto MCC, MgO & Aerosil 200 carrier due to high loading efficiency and solid SMEDDS were being filled in HGC.
S. No. Formulation (F) Adsorbent (A) loading capacity(F:A) 1
A2 (Atorvastatin)
MCC pH 101 1:10
2 Magnesium oxide 1:5
3 Aerosil 200 1:0.8
Table 5.14 Amount of Adsorbent required 5.10 Characterization pf Solid SMEDDS of Atorvastatin
5.10.1 Micromeritics Properties of Solid SMEDDS
All Solid SMEDDS formulations were found to be free flowing white powder. Micromeritics Properties like Angle of repose, BD, TD, CI and HR are tabulated.
Formulation Angle of repose Ɵ BD (g/mL) TD (g/ml) CI (% ) HR ATV MCC 26.56±0.08 0.89±0.02 1.13±0.03 21.24±0.02 1.27±0.05 ATV MgO 19.65±0.02 0.83±0.03 1.02±0.02 18.63±0.05 1.23±0.03 ATV Aerosil 19.65±0.02 0.83±0.03 1.02±0.02 18.63±0.05 1.23±0.03
*values mean ± SD (n=3)
Table 5.15 Micromeritic Study of Solid SEDDS 5.10.2 Drug Content
Results of % drug content of Solid SMEDDS were tabulated.
Tab.5.16 Drug content of solid SMEDDS
.
Drug content of solid SMEDDS prepared by carrier MCC i.e. ATV MCC were higher in comparison to % drug content of solid SMEDDS prepared by carrier Aerosil 200 (ATV Aerosil) & prepared by carrier MgO (ATV MgO).Although difference was not too much drastic in them, This suggested that MCC as a adsorption carrier to liquid SMEDDS gives better results in comparison to Aerosil 200 & MgO as adsorption carrier to liquid SMEDDS 5.10.3 % Transmittance
S. No. Formulation % Transmittance
1 ATV MCC 93.61
2 ATV Aerosil 82.36
3 ATV MgO
Table 5.17 % Transmittance of reconstituted solid SMEDDS
*values mean ± SD (n=3)
From the table, % Transmittance of all reconstituted Solid SMEDDS found in range of 90 to 100%. % Transmittance of reconstituted solid SMEDDS prepared using adsorbing MCC is very near to 100%. Reconstituted solid SMEDDS prepared using adsorbing Aerosil 200 showed signs of turbidity while that of MCC were clear and this might be due to un-dissolved aerosil 200 particles after reconstitution. Therefore MCC as an adsorbent carrier does not affect performance of % Transmittance while Aerosil 200 affects slightly.
5.10.4 In-Vitro dissolution studies of solid SMEDDS
A. In-vitro dissolution study of solid SMEDDS of Atorvastatin
Dissolution of Solid SMEDDS ATV MCC, ATV Mgo, Atorvastatin and marketed tablet of Atorvastatin (20 mg) were done at pH 1.2 buffer medium.
Results of CPR of Solid SMEDDS formulations of Atorvastatin are shown in Table and Figure
S .No. Formulation % Drug Content
1 ATV MCC 93.61
2 ATV Aerosil 82.36
3 ATV MgO 86.12
*values mean ± SD (n=3), ** based on liquid SMEDDS (L2) in same medium as reference,! Is with reference to marketed tablet, @ is with reference to drug
Table 5.18 Dissolution of Atorvastatin from solid SMEDDS LOV A, LOV N, marketed tablet and drug in pH 1.2
From the table and figures of in vitro dissolution of Atorvastatin from Solid SMEDDS ATV MCC, ATV MgO, marketed tablet of Atorvastatin (20 mg) and active drug in 1.2 pH, it was found that rate and extent of atorvastatin release from all formulations, the solid SMEDDS ATV MCC & ATV MgO were considerably high as compared to marketed tablet and pure drug. It recommended that ATV MCC &
ATV MgO resulted in spontaneous microemulsion formation with smaller droplets, which results in rapid rate and higher extent of drug release than marketed tablet into the aqueous phase.
In-vitro dissolution of Solid SMEDDS of atorvastatin prepared using MCC (ATV MCC showed 98.7 % drug release within 30 min, while In-vitro dissolution of Solid SMEDDS of atorvastatin prepared using MgO (ATV MgO) showed 88.08 % drug release in 30 min. Maximum drug release achieved 99.45% from ATV MCC and 96.11% from ATV MgO in 60 min in pH 1.2.
6 OBJECTIVE OF THE STUDY:
Improvement in solubility, there by means of dissolution and healing performance of poorly water soluble hypolipidemic agent Atorvastatin.
Formula and improvement of the liquid SEDDS for Atorvastatin and comparing its in vitro overall performance.
System and improvement of the strong SEDDS of Atorvastatin Liquid SEDDS and evaluating its in vitro performance.
7 RECOMMENDATIONS
Liquid or even solid SE system may be recommended for development of low solubility and occasional variable oral relative bioavailability for lipophilic capsules, which can be used to enhance fee and the volume of relative bioavailability.
Due to advanced fee and quantity of launch in vitro and in vivo, it could give better therapeutic outcomes, low side results, better effectiveness in less dose &
better affected person compliance.
Those structures can be commercialized as new formulations on this everyday marketplace. Further research is suggested for research scientist and for industry for development of recent drug packages as a extensive a success scope.
So, This SE system can be endorsed to make use of by using scientists, patients and even enterprise factors.
8 FUTURE SCOPE
Those formulations may additionally similarly be scaled up in futures for industrial exploitation. Final formulations will also be evaluated for pharmacodynamics look at and in vivo medical studies on humans.
Greater thoughts must be thrilled for the traits of a number of lipid formulations existing, such that a few tips and the experimental techniques may be diagnosed which help to become aware of t strategies should be evolved to music the drug solubilization kingdom in vivo, and even in-vitro techniques are also needed to predict the energetic changes shaped inside the intestine.
Bodily & chemical balance of the medication within lipid primarily based dosage and lipid dosage compatibility with the capsule shells desires to be studied.
The future studies on this have to be given priorities for human bioavailability checks or even for the basic mechanistic research of this type of captivating and various formulation organization.
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