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71 AN ANALYTICAL AND EXPERIMENTAL RESEARCH FOR FORMULATION OF SELF
EMULSIFYING DRUG DELIVERY SYSTEM: A REVIEW Yogendra Kumar Dube
M. Pharm Student, Bhabha Pharmacy Research Institute Prof. Rishikesh Sharma
Bhabha Pharmacy Research Institute 1 ORAL DRUG DELIVERY
(Vieth, M. C. et al. 2004)
Oral runs as the primary drug ingestion course for lots diseases now a day and even first line for brand spanking new dosage tendencies. Oral is commonplace
& convenient shipping path because of ease in ingestion, incredibly affected person compliant, no sterile stress, cheapness & ease in dosage designing. So major generic groups are turning much to manufacture bioequivalent oral formulations. Oral preparations faces the low and even inconsistent bioavailability issues due to low aqueous solubility. This leading to greater inter-intra problem variant, dose percentage hassle and lastly therapeutic impact disintegrate. Drug solubility & permeability, efflux mechanisms inclination, dissolution charge, first-skip & pre-systemic metabolism are different factors which impacts oral bioavailability of drug product the most important motives of low oral bioavailability are low solubility &
permeability.
1.1 Solubility (Parve B. et al., 2014)
The time period “solubility” is defined as most amount of solute that may be dissolved in a given quantity of solvent.
Quantitatively it is defined because the awareness of the solute in a saturated answer at a certain temperature. In qualitative terms, solubility may be defined as an interaction of or extra substances to form a homogenous molecular dispersion. Solubility of a drug substance performs a high role in controlling its dissolution from dosage shape. Aqueous solubility of a drug is a chief component which determines its dissolution charge.
Term (soluble) Part of solvent required per solute
Very < 1
Freely 1 to 10
Sparingly 30 to 100
Slightly 100 to 1000
Very slightly 1000 to 10,000 Practically insoluble ≥ 10,000
Table 1.1 Solubility Criteria 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
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72 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.
Palamakula, A.et. al. (2004) obtained a systematic model of factors yielding an optimized selfnano emulsified system made capsule of a lipophilic drug Co enzyme Q10. Optimization was done using 3 factors and 3 levels by using independent variables like amount of limonene, surfactant and co-surfactant by a statistical design. The cummulative%
drug release, particle size, zeta potential, turbidity was dependent variables. In response surface methodology, observed
& predicted values lied in the close conformity. Hence, technique showed formulation with > 90% release within 5 min with low turbidity and low particle size.
Subramanian, N. et. al (2004) Developed a SMEDDS of BCS Class II drug, Celecoxib forenhancement in its solubility & bioavailability orally and for achieving onset of action rapidly.
Celecoxib have low solubility and high variability in absorption. Optimized SMEDDS composed of 49.5% oil, 40.5%
surfactant/co-surfactant (3:1) and 10%
drug and optimization was done by simplex lattice design. Formulation proven significantly high absorption rate
& extent of absorption with 132%
bioavailability than conventional capsule.
It concluded that mixture design was suitable for optimization of SMEDDS.
Patil, P., & Paradkar, A. (2006) formulated a SE containing loratadine and also showed th epotential of carrier PPB for solidification. Formulated SES composed of 63% Captex 200, 16%
Cremophore EL, 16% Capmul MCM and 5% drug loratadine. SES was evaluated for characterization parameters. System loaded in PPB by solvent evaporation.
SES-loaded PPB were characterized using SEM, surface area (BET), load efficiency of carrier, drug release. After loading, surface area decreased significantly, indicates filling of SES into PPB. Drug release was dependent on leaching of SES from PPB. Here, bead size and its pore managed the load capacity and even loratadine release from PPB.
Patel, A. R., & Vavia, P. R. (2007) formulated a fenofibrate SMEDDS and evaluated in vivo-vitro potential.
Fenofibrate solubility in different vehicles like oils, surfactants was checked to select them and ternary phase diagrams evaluated the microemulsion area.
SMEDDS checked for emulsifying properties, clarity, and precipitation test and particle size distribution. The optimized SMEDDS composed of 31.5%
Labrafac CM10, 47.3% Tween 80 and 12.7% PEG 400, which given completed release in 15 min compared to drug fenofibrate. The final SMEDDS reduced serum lipid levels significantly compared to plain drug fenofibrate. The final optimized SMEDDS was stable upto 12 months as per ICH guidelines.
Patel, D., & Sawant, K. K. (2007):
developed SMEDDS for enhancement of bioavailability ofhydrophobic anti-viral drug acyclovir, used in Herpes Simplex Virus (HSV) infections. SMEDDS were characterized for its dilution test, pseudo ternary phase diagrams, % T, phase separation & others. Optimized SMEDDS containing acyclovir, Tween 60 surfactant, glycerol co-solvent and sunflower oil was compare to drug solution in rats.
Bioavailability was increased by 3.5 fold compared to drug solution.
Sheikh, S. et al. (2007) prepared nanoemulsion of poorly soluble antihypertensive drug ramiprilby titration method. Based on solubility study, oil Sefsol 218 was being selected. For the formulation composed of oil (20%), Smix (27%) and water phase (53%V/V) gave polydispersibility index minimum and 34.5nm droplet size. Hence, nanoemulsion, have high solubilization capacity and thermodynamic stability compared to other micellar solution or dispersion. So, it can be promising approach to enhance solubility of poorly soluble drugs. Ternary phase diagrams were used to select the proper ratios of excipients.
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73 Wei, L. et. al (2007): developed
carvedilol Self-emulsifying osmotic pump tablet (SEOPT)which improved oral bioavailability of drug carvedilol by controlling the rate of release and by making plasma concentrations stability high. DSC, TEM, IR, XRD and particle size determination showed carvedilol in amorphous form and round shaped globules in emulsion. The drug release at 12 hr was found 85.18%. Carvedilol bioavailability was found 156.78%
compared to Luode® in dogs and IVIVC obtained. Therefore, carvedilol SEOPT was successful
Mandawgade, S. D. et al. (2008) formulated SMEDDS of lipophilic ant malarial Artemetherusing N-LCT as oil as well as Capryol 90 commercially available oil both and then characterized for globule size and drug release compared to its marketed Larither®. In vivo anti- malarial performance like % parasitemia, animal survival time and its activity was checked for SMEDDS and Larither® in the infected mice. Self-emulsification was excellent in both. SMEDDS released drug
>98% in 15 min and Larither® showed 46% in 60 min. SMEDDS globule size found to bev <100 nm. It concluded SMEDDS of Artemether can be used for anti-malarial effect and that natural oil can be used in further developments.
Atef, E. & Belmonte, AA (2008):
developed and characterized phenytoin SEDDS & also compared its bioavailability with Dilantin®. Dissolution study showed considerable progress in drug release and in-vivo test given improvement in drug absorption from SE formulation compared to Dilantin®.
Stable formulation was optimized.
Balakrishnan, P. et al. (2009):
formulated a solid SE system by spray drying of liquid system on aerosil 200 for increase in dexibuprofen bioavailability.
Liquid SE system composed of drug &
excipients (Capryol 90, Labrasol &
Labrafil). No change in particle sizes of liquid & solid SE system emulsion found.
The solid SE system was evaluated using studies like DSC, SEM and XRD. In vivo of solid SE system & drug powder showed that initial drug plasma conc in solid SE system were notably high compared to drug powder. AUC & Cmax of solid SE system were high compare to drug. It
meaned that solid SEDDS improved its dexibuprofen bioavailability.
Nepal, P.R. et al. (2010) formulated hydrophobic drug Coenzyme Q10 into SNEDDS to reducethe problem of its low bioavailability. Solubility study selected Witepsol® H35, Solutol® HS15 and Lauroglycol® FCC excipients. Phase diagram identified nano emulsifying area and optimization of SNEDDS was done.
The optimized formulation composed of CoQ10, Witepsol® H35, Solutol® HS15 and Lauroglycol® FCC in the ratio of 1:0.7:4:2, respectively. The stability study of the optimized SNEDDS in both buffers pH 1.2 & 6.8 showed no pH effect on droplet size. In vitro dissolution test and its in vivo animal study of SNEDDS concluded improvement in bioavailability of poorly soluble Co enzyme Q10.
Wankhade, V. et. al. (2010):
developed SNEDDS of poorly bioavailable Gliclazide, anti-diabetic drug having pH dependant solubility. Solubility of Gliclazide in oil and surfactants were determined to get SNEDDS components.
Phase diagrams were being generated to spot micro/nano emulsification area. The optimized SNEDDS needed surfactant content less than 55% and yielded nanoemulsion of mean globule size 146 nm, that was not affected by the pH of medium and Gliclazide. The optimized SNEDDS released the drug completely within 20 min irrespective of pH.
Patel, M. J. et al. (2010):
developed novel lovastatin SMEDDS, BCS II drug have very low 50%oral bioavailability. Solubility study was performed for selection of excipients on basis of saturated solubility study.
Microemulsion area was generated by phase diagram. Drug-excipients compatibility was checked by DSC and FTIR testing. Final formulation was with droplet size 18 to 24 nm. This provided good drug solubility & stability (in HCl &
water) and also enhanced lovastatin release compare to its marketed tablet.
3 SUMMARY
Oral path is a fave one in chronic remedy.
Approx 35‐forty% NCE has low aqueous solubility. Their oral shipping is majorly associated with troubles like terrible bioavailability, inter-intra difficulty variant & dose share.
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VOLUME: 07 Issue 04 Paper id-IJIERM-VII-IV June 2020
74 To surmount them, new strategies
used to enhance solubility &
bioavailability, which incorporates β-CD complicated, stable dispersion, micronising, co‐precipitation, salt shape, emulsion, micelle, nano-debris and so forth, but they are associated with their personal set of difficulties and issues.
Micronisation faces chemical instability hassle, strong dispersion makes dosage form bulky, which is very hard to swallow by means of sufferers. In complexation, drug should be solubilized in each aqueous and non-aqueous solvent.
4 CONCLUSION
The primary observes objectives are finished that system and assessment of self-emulsifying components containing poorly soluble tablets like Atorvastatin. In this have a look at liquid SMEDDS of BCS elegance II tablets having low and variable bioavailability were effectively prepared.
Solidification of liquid SMEDDS changed into performed by adsorption method with distinctive providers, from which MCC proved as the first-rate carrier.
Due to solidification, formula turns into greater strong, reproducible, affected person compliant and clean to handle compared to liquid without compromising its self-emulsifying belongings, in-vitro dissolution.
4.1 Limitations of Research Work Quantity of surfactant and co-surfactants to be used in this have a look at were high, so toxicity examine, in vivo medical look at on people and pharmacodynamic observe is lacking yet. Even though they were managed by using GRAS listing and IIG limits, they needed a good deal attention.
Solidification of liquid SE machine turned into vital and of subjective give up point. Existence of strong providers having high loading of liquid SE gadget is low. Limited vendors got successful in solidification of device.
Till date in India, a few countable numbers of oral SE formulations are in market examine to other traditional oral formulations like tablets, pills and so forth. The drug candidate formulations at the start level.
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