Self-Microemulsifying Drug Delivery System of Phillygenin: Formulation Development, Characterization and Pharmacokinetic Evaluation

Phillygenin, as an active ingredient of Forsythia suspensa, possesses a wide range of biological and pharmacological activity. However, its development and application are restricted due to its poor bioavailability and low solubility. Our work aimed to develop a self-microemulsifying drug delivery system to improve the oral bioavailability of phillygenin. The composition of the self-microemulsifying drug delivery system was preliminary screened by the pseudo-ternary phase diagram. Subsequently, the central composite design method was employed to optimize the prescription of the self-microemulsifying drug delivery system loaded with phillygenin. The prepared self-microemulsifying drug delivery system of phillygenin was characterized in terms of morphology, droplet size distribution, polydispersity index and stability. Then, the in vitro dissolution and the oral bioavailability were analyzed. The optimized self-microemulsifying drug delivery system of phillygenin consisted of 27.8% Labrafil M1944CS, 33.6% Cremophor EL, 38.6% polyethylene glycol 400 (PEG-400) and 10.2 mg/g phillygenin loading. The prepared self-microemulsifying drug delivery system of phillygenin exhibited spherical and uniform droplets with small size (40.11 ± 0.74 nm) and satisfactory stability. The in vitro dissolution experiment indicated that the cumulative dissolution rate of the self-microemulsifying drug delivery system of phillygenin was significantly better than that of free phillygenin. Furthermore, after oral administration in rats, the bioavailability of phillygenin was significantly enhanced by the self-microemulsifying drug delivery system. The relative bioavailability of the self-microemulsifying drug delivery system of phillygenin was 588.7% compared to the phillygenin suspension. These findings suggest that the self-microemulsifying drug delivery system of phillygenin can be a promising oral drug delivery system to improve the absorption of phillygenin.

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Formulation and Evaluation of Self Nanoemulsifying Drug Delivery System of Nifedipine

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v5i4.8881 ◽

2015 ◽

Vol 5 (4) ◽

Author(s):

Dinesh Kaushik ◽

Jyoti Malik ◽

Satish Sardana ◽

Chisa Matsubara

Keyword(s):

Drug Delivery ◽

Dissolution Rate ◽

Drug Delivery System ◽

Delivery System ◽

Ternary Phase Diagram ◽

In Vitro Dissolution ◽

Oral Drug ◽

Drug Bioavailability ◽

Wide Range

Oral route is the most preferred route of drug administration due to its easy accessibility, intake, and wide range of choices making it economical. Currently, greater than 60% of marketed drugs are oral products. Over 90% of therapeutic compounds given orally areknown to possess oral bioavailability limitations. Therefore, there is a need to explore various approaches that can be used to improve oral drug bioavailability besides using physical and chemical means. The objective of this study is to prepare a formulation i.e. self microemulsifying drug delivery system (SMEDDS) of nifedipine with the intention to improve the increase dissolution rate (solubility). This will ensure the quick absorption and uniform bioavailability of nifedipine. Selection of oils, surfactants and co-surfactants was done by determining % transparency and on the basis of compatibility studies by FTIR spectra analysis. Different SMEDDS formulation were prepared of different ratio of oil:surfactantmix (1:9,2:8,3:7,4:6,5:5,6:4,7:3,8:2,9:1) and different ratio of surfactants : cosurfactants. Pseudo ternary phase diagram were constructed by water titration method to obtain a particle micro-emulsion region (on the basis of clarity and transparency). The formulation B-I was optimized because of maximum transparency (87.35%) and maximum % drug entrapment (95.32%). The average droplet size and zeta potential was found 86.05 and -0.189. The solubility of nifedipine increase in SMEDDS formulation upto72.17%.From in vitro dissolution study it was proved that SMEDDS formulation releases drug at faster rate, thus the objective of increase solubility and hence the better dissolution rate for uniform bioavailability via SMEDDS formulation of nifedipine was successfully achieved.

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Enhanced Oral Bioavailability and Improved Biological Activities of a Quercetin/Resveratrol Combination Using a Liquid Self-Microemulsifying Drug Delivery System

Planta Medica ◽

10.1055/a-1270-7606 ◽

2020 ◽

Author(s):

Patcharawalai Jaisamut ◽

Subhaphorn Wanna ◽

Surasak Limsuwan ◽

Sasitorn Chusri ◽

Kamonthip Wiwattanawongsa ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Oral Bioavailability ◽

Biological Activities ◽

Area Under The Curve ◽

Aqueous Solubility ◽

The Self

AbstractBoth quercetin and resveratrol are promising plant-derived compounds with various well-described biological activities; however, they are categorized as having low aqueous solubility and labile natural compounds. The purpose of the present study was to propose a drug delivery system to enhance the oral bioavailability of combined quercetin and resveratrol. The suitable self-microemulsifying formulation containing quercetin together with resveratrol comprised 100 mg Capryol 90, 700 mg Cremophor EL, 200 mg Labrasol, 20 mg quercetin, and 20 mg resveratrol, which gave a particle size of 16.91 ± 0.08 nm and was stable under both intermediate and accelerated storage conditions for 12 months. The percentages of release for quercetin and resveratrol in the self-microemulsifying formulation were 75.88 ± 1.44 and 86.32 ± 2.32%, respectively, at 30 min. In rats, an in vivo pharmacokinetics study revealed that the area under the curve of the self-microemulsifying formulation containing quercetin and resveratrol increased approximately ninefold for quercetin and threefold for resveratrol compared with the unformulated compounds. Moreover, the self-microemulsifying formulation containing quercetin and resveratrol slightly enhanced the in vitro antioxidant and cytotoxic effects on AGS, Caco-2, and HT-29 cells. These findings demonstrate that the self-microemulsifying formulation containing quercetin and resveratrol could successfully enhance the oral bioavailability of the combination of quercetin and resveratrol without interfering with their biological activities. These results provide valuable information for more in-depth research into the utilization of combined quercetin and resveratrol.

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Development of a self-microemulsifying drug delivery system of domperidone: In vitro and in vivo characterization

Acta Pharmaceutica ◽

10.2478/acph-2013-0013 ◽

2013 ◽

Vol 63 (2) ◽

pp. 241-251 ◽

Cited By ~ 9

Author(s):

Ramesh Jakki ◽

Muzammil Afzal Syed ◽

Prabhakar Kandadi ◽

Kishan Veerabrahma

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Oral Bioavailability ◽

Ternary Phase Diagram ◽

Water Soluble ◽

In Vitro Dissolution ◽

Size Analysis

The main objective of this work was to prepare a self-micro emulsifying drug delivery system (SMEDDS) for enhancement of oral bioavailability of domperidone, a poorly water soluble drug. The solubility of the drug was determined in various vehicles. A pseudo ternary phase diagram was constructed to identify the self-micro emulsification region. The in vitro self-micro emulsification properties and droplet size analysis of SMEDDS were studied following their addition to water under mild agitation. Further, the resultant formulations were investigated for clarity, phase separation, globule size, effect of pH and dilutions (1:100, 1:500, 1:1000) and freeze-thaw stability. The optimized formulation, SMEDDS-B used for in vitro dissolution and bioavailability assessment, contained oil (Labrafac CC, 25 %, m/m), surfactant (Tween 80, 55 %, m/m), and co-surfactant (Transcutol®, 20 %, m/m). The preliminary oral bioavailability of domperidone from SMEDDS was 1.92-fold higher compared to that of domperidone suspension in rats. The AUC0-24 and cmax values were 3.38 ± 0.81 μg h mL-1 and 0.44 ± 0.03 μg mL-1 for SMEDDS-B formulation in comparison with 1.74 ± 0.18 μg h mL-1 and 0.24 ± 0.02 μg mL-1 for domperidone suspension, suggesting a significant increase (p < 0.05) in oral bioavailability of domperidone from SMEDDSS.

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Quality-By-Design-Based Development of a Voxelotor Self-Nanoemulsifying Drug-Delivery System with Improved Biopharmaceutical Attributes

Pharmaceutics ◽

10.3390/pharmaceutics13091388 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1388

Author(s):

Aristote B. Buya ◽

Romano Terrasi ◽

Jérémie K. Mbinze ◽

Giulio G. Muccioli ◽

Ana Beloqui ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Oral Bioavailability ◽

Oral Delivery ◽

Ternary Phase Diagram ◽

Desirability Function ◽

Limiting Factors ◽

In Vitro Dissolution

Low aqueous solubility and poor oral bioavailability are limiting factors in the oral delivery of voxelotor, an antisickling agent. To overcome these limitations, a voxelotor self-nanoemulsifying drug delivery system was developed. Various oils, surfactants, and cosurfactants were screened for their solubilization potential for the drug. The area of nanoemulsification was identified using a ternary phase diagram. An experimental mixture design and a desirability function were applied to select SNEDDSs that contain a maximum amount of lipids and a minimum amount of surfactant, and that possess optimal emulsification properties (i.e., droplet sizes, polydispersity index (PDI), emulsification time, and transmittance percentage). The optimized SNEDDS formulation was evaluated for the self-emulsifying time (32 s), droplet size (35 nm), and zeta potential (−8 mV). In vitro dissolution studies indicated a 3.1-fold improvement in drug solubility from the optimized SNEDDS over pure drug powder. After 60 min of in vitro lipolysis, 88% of the voxelotor loaded in the SNEDDS remained in the aqueous phase. Cytotoxicity evaluation, using Caco-2 cells, indicated the safety of the formulation at 0.9 mg/mL. The transport of the voxelotor SNEDDS across Caco-2 monolayers was significantly enhanced compared to that of the free drug. Compared to the drug suspension, the developed SNEDDS enhanced the oral bioavailability (1.7-fold) of voxelotor in rats. The results suggest that further development of SNEDDSs for the oral delivery of voxelotor is needed.

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Applicability of Gum Karaya in the Preparation and in Vitro Evaluation of Losartan Potassium as Chronotherapeutic Drug Delivery System

Journal of Scientific Research ◽

10.3329/jsr.v7i1-2.21182 ◽

2015 ◽

Vol 7 (1-2) ◽

pp. 65-74

Author(s):

K. Latha ◽

V. V. Srikanth ◽

S. A. Sunil ◽

N. R. Srinivasa ◽

M. U. Uhumwangho ◽

...

Keyword(s):

Drug Delivery ◽

Tensile Strength ◽

Drug Delivery System ◽

Delivery System ◽

Lag Time ◽

Losartan Potassium ◽

In Vitro Dissolution ◽

Burst Release ◽

Gum Karaya

The objective of this investigation is to study the applicability of gum karaya, the natural gum for the preparation and in vitro evaluation of losartan potassium, as Chronotherapeutic Drug Delivery System (ChDDS). The compression-coated timed-release tablets (CCT) containing losartan potassium in the core tablet were prepared by dry coating technique with different ratios of gum karaya as the outer coat. The parameters investigated were tensile strength, friability, in vitro dissolution studies and drug concentration. The optimized formulation was further characterized by powder XRD and FTIR to investigate interactions and no interactions observed. The tensile strength and friability of all the CCT were between 1.06-1.23 MN/m2 and < 0.3% respectively. All the CCT showed a clear lag time before a burst release of drug. However, the lag time of drug release increased as the amount of gum karaya in the outer layer increased. For instance, the lag time of LGK1, LGK2, LGK3, LGK4, LGK5, LGK6 and LGK7 were 16, 10.5, 5.5, 3, 2, 1.5 and 0.5 hrs respectively. The drug content of all the CCT was >98%. Formulation LGK3 was taken as an optimized formulation which can be exploited to achieve ChDDS of losartan potassium for the treatment of hypertension.

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SELF-EMULSIFYING DRUG DELIVERY SYSTEM CONTAINING ACECLOFENAC: DESIGN & DEVELOPMENT USING QUALITY BY DESIGN (QBD) CONCEPT

INDIAN DRUGS ◽

10.53879/id.51.06.p0016 ◽

2014 ◽

Vol 51 (06) ◽

pp. 16-26

Author(s):

V Suthar ◽

◽

M Gokel ◽

S Butani ◽

A Solanki

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Dosage Form ◽

Quality By Design ◽

Tween 80 ◽

Current Approach ◽

In Vitro Dissolution ◽

Design Development

The aim of the present study was to develop self-emulsifying drug delivery system (SEDDS) of aceclofenac for potential improvement in the in vitro dissolution. The Food and Drug Control Agency (FDCA) has put more stress on the quality, safety and efficacy of the dosage form. The use of design of experiments and quality by Design (QbD) in the development of self emulsifying drug delivery system (SEDDS) containing aceclofenac is demonstrated. The optimum formulation contained Labrafil M 1944 CS, Tween 80 and Transcutol P. The systematic approach enabled us in identifying the design space. The results revealed that while devising the control strategies during manufacturing, more attention should be focused on the ratios of oil to surfactant and surfactant to co-surfactant. The drug was released at a faster rate due to a large surface area. The current approach enabled us to develop a dosage form which is economic, patient-friendly and does not require assistance of a doctor or nurse, especially at remote places at odd hours.

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DEVELOPMENT AND EVALUATION OF ZIPRASIDONE LOADED SOLID SELF-MICRO EMULSIFYING DRUG DELIVERY SYSTEM

INDIAN DRUGS ◽

10.53879/id.57.08.12632 ◽

2020 ◽

Vol 57 (08) ◽

pp. 53-60

Author(s):

Purushottam Patil ◽

Malik Shaikh ◽

Paresh Mahaparale

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Physical Adsorption ◽

Gastrointestinal Transit ◽

Water Soluble ◽

In Vitro Dissolution ◽

Scanning Calorimetry ◽

Poorly Water Soluble

Solid self-micro emulsification technique is the new approach for poorly water-soluble and poorly bioavailable drugs by allowing the drug substance to be incorporated into the oil phase and thus having the ability to permeate the GI membrane to a faster extent. Oleic acid, Tween 80, methanol and colloidal silicon dioxide were used as penetrant, surfactant, co-surfactant and adsorbent, respectively. The interaction between drug and excipients was examined by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The results of DSC and FTIR studies did not reveal any possible drug-excipient interactions. The conversion of liquid self-microemulsifying drug delivery system (SMEDDS) into the solid SMEDDS increases the stability of the emulsion formulation achieved by physical adsorption of an adsorbent material. The release of drug from SMEDDS formulation is justified by in-vitro dissolution studies. SMEDDS increases the solubility of the drug and improves the bioavailability, without disturbing gastrointestinal transit. SMEDDS has the potential to provide a useful oral solid dosage form for the poorly water-soluble drug ziprasidone.

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