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Vol 2 | Issue 2 | Apr – Jun 2023                                                                                     Indian J Pharm Drug Studies | 82 

Original Article 

Characterization of Liquid Oral Containing Lycopene Phytosomes for 

Improved Absorption 

Viresh K Chandur1, Ramkrishna Shabaraya A2 

From 1* Asso. Prof. 2 Prof. Principal, Department of Pharmaceutics, Srinivas College of Pharmacy Mangalore. 

Correspondence to: Viresh K Chandur, Asso. Prof. Department of Pharmaceutics, Srinivas College of Pharmacy, Mangalore. Tele: 

9742565141, Email: viresh.chandur2009@gmail.com  

ABSTRACT 

Objective: Owing to life style modifications and use of Nutraceuticals present study was aimed to develop stable and controlled 

release oral liquid containing lycopene phytosomes for better therapeutic activity. Tomatoes are consumed raw or in the processed 

forms like Ketchup, Sauce, Soup and salad. The global lycopene market size was valued at $107.2 million in 2020, and is projected 

reach $187.3 million in 2030, registering a CAGR of 5.2% from 2021 to 2030. It has several medicinal properties, which has 

increased its demand in the Nutraceutical market. Method: Extracted lycopene was complexed with phospholipid (1:1) to form 

phytosomes and subjected to pre and post evaluations of liquid oral nanosuspension (LPS1 to LPS4) containing different 

concentration of Sodium Carboxymethylcellulose, and Hydroxy Propyl Methyl Cellulose K4M Results: Acceptable results were seen 

for pre evaluation for FTIR, DSC compatible studies and post evaluation like pH(4.4 to 5.1), viscosity (15.2 to 42.2 cp), Drug content 

(96.5 to 98.8%), specific gravity (1.1042 to 1.1062), Particle size(450.5 to 594.5nm) and zeta potential (-21.2 to -23.2) respectively. 

Conclusion: Overall LPS3 was found to be better and stable formulation containing 10ml of 1% HPMC K4M as suspending agent. 

Anti-Oxidant property was found comparatively same for plain and complexes of lycopene, difference was found for duration of 

antioxidant activity which can be correlated with in-vitro dissolution studies. 

Key words: Lycopene, Liquid Oral, Anti-Oxidant, Nutraceutical, Phytosomes. 

ecent studies have an impact on how people feel 

about using dietary supplements, and consumer 

interest in self-care is rising [1]. The potential of 

complementary and alternative medicine—these so-called 

"community-based lifestyle interventions"—to prevent 

diseases has been the subject of a growing body of scientific 

research over the past ten years. One of the active components 

derived from a natural source is lycopene [2]. Lycopene, a 

chemical with a high lipophilicity, has a variety of 

pharmacological effects. Its bioavailability is however 

constrained by its poor water solubility and significant pre-

systemic metabolism. Due to their poor oral bioavailability, 

many barriers prevent the medical use of medications derived 

from herbs, especially those that include polyene chains with 

35–40. Carbon atoms in their chemical structure. The use of 

phytosomal technology is one approach to address these more 

recent issues. Lycopene and the consumption of foods 

containing lycopene may impact the risk of cancer or 

cardiovascular disease, according to encouraging results from 

epidemiological, cell culture, and animal research, but more 

clinical trial data is required to support this idea [3].  

A unique herbal formulation called a phytosome, which 

resembles a tiny cell, combines the bioactive 

phytoconstituents of an herb extract complexed with 

phospholipids echnique is a ground-breaking approach for 

dramatically ito create lipid-compatible molecular complexes. 

This phytosome tmproving bioavailability, substantially 

increasing clinical benefit, assuring delivery to the tissues, and 

maintaining nutrient safety. Over traditional botanical extracts, 

phytosomes offer superior pharmacokinetic and 

pharmacodynamic behaviour. This method made use of the 

complex formation that can occur when phospholipid 

molecules interact with herbal extracts or their constituents to 

create a lipid-compatible molecular complex that is soluble in 

both a lipid environment and water [4]. Delivering an effective 

level of the active components is necessary for any herbal 

product to be effective. This problem is solved by the 

phytosome technology, which significantly increases the 

bioavailability of phytomedicines [5]. 

MATERIALS & METHODS 

Tomatoes were collected from local market at Mangalore of 

Karnataka in the month of January 2018 and authenticated by 

Pilikula Nisarga Dhama (Botanical garden) Mangalore. 

Natural or synthetic phospholipids, such as 

phosphatidylcholine, were obtained from Hi media, aprotic 

R 

mailto:viresh.chandur2009@gmail.com


Chandur & Shabaraya A                                                  Containing Lycopene Phytosomes for Improved Absorption 

 

Vol 2 | Issue 2 | Apr – Jun 2023                                                                                     Indian J Pharm Drug Studies | 83 

solvent, such as dioxane or acetone, n-hexane, ethanol were 

obtained by Merck chemicals.  

Preparation of oral Nanosuspension containing Lycopene 

Phytosomes: This preparation is majorly includes two steps. 

Extraction and Preparation of Lycopene Phytosomes was done 

as per Aghel N et al., 2011 and Jain S et al., 2019 respectively 

[6, 7] and composition of Suspension containing Lycopene 

Phytosomes was prepared as per Table 1. 

Table 1: Composition of Liquid Orals 

Ingredients LPS1 LPS2 LPS3 LPS4 

Lycopene 

Phytosomes 

equivalent to  

10mg / 

5ml. 

10mg / 

5ml. 

10mg  / 

5ml. 

10mg  / 

5ml. 

Simple Syrup 10 ml 10 ml 10 ml 10 ml 

Glycerin 10 ml 10 ml 10 ml 10 ml 

Aqueous Solution 

of Na-CMC (1%) 

5 ml 10 ml - - 

Aqueous solution 

of HPMC K4M 

(1%) 

- - 5 ml 10 ml 

Methyl Paraben 

(%) 

0.09 0.09 0.09 0.09 

Propyl Paraben 

(%) 

0.01 0.01 0.01 0.01 

Purified Water 50 ml 50 ml 50 ml 50 ml 

Preparation of Lycopene Phytosomal Suspension dosage 

form: To lower the interfacial tension between liquid and air, 

the powdered form of the medication complex was completely 

moistened with syrup and glycerin solution. The wetted 

material was then slowly added to, with continuous triturating, 

the suspending agents such as sodium carboxy methyl 

cellulose (Na-CMC) or hydroxy propyl methyl cellulose K4M 

in the aqueous medium containing specified preservatives. In 

order to create four different suspension formulations, LPS1, 

LPS2, LPS3, and LPS4, 5 and 10 millilitres of 1% aqueous 

Na-CMC and HPMC K4M solution, respectively, were used. 

Lastly, a continuous trituration process was used to raise the 

suspension to the final volume using filtered water in order to 

produce a uniform product. The production quality of all four 

suspension formulations was then assessed in accordance with 

established guidelines. [8]. 

Formulation of Lycopene Phytosome Liquid Orals 

 
Fig 1: Lycopene Phytosomal Liquid Orals. 

Evaluation of Lycopene Phytosomes Suspensions: 

Evaluation of Suspension: All the four Suspension dosage 

form (LPS1, LPS2, LPS3 and LPS4) were evaluated for pH, 

viscosity, Drug content, Drug Release studies and stability 

study of the final suspension was carried out.  

pH: Using common buffer solutions, such as pH 4 and 7, the 

pH metre was calibrated. The pH of the suspension was tested 

after it had been dissolved in 50.0 ml of distilled water in an 

amount of about 5 ml. With the use of a Systronic Digital pH 

metre, the pH of the samples was determined. 

Viscosity: Using a Brookfield Viscometer, the sample's 

viscosity was measured (DV - E Model). A tiny volume 

holder was used to hold the necessary amount of suspension, 

and the LV4-27 spindle with a 100 rpm rotational speed was 

employed. Centipoises (cp) and the associated percent torque 

value were recorded. 

Specific Gravity: Relative density, or specific gravity, is the 

ratio of the density (mass of a unit volume) of a substance to 

the density of a given reference material. Specific gravity 

usually means relative density with respect to water [9].  

Determination of drug content: Accurately 5mL of 

formulation from different batches was measured and 

transferred to 100 mL volumetric flask. To this 50-70mL of 

0.1 N HCl was added and sonicated for 30 min. Volume was 

adjusted to 100mL. Complete dispersion of contents was 

ensured visually and the dispersion was filtered using 

Whattman Filter Paper. From this solution, 1 mL of sample 

was withdrawn and diluted to 10mL with 0.1 N HCl. Contents 

of lycopene was measured at maximum absorbance at 471nm 

using Jasco UV Spectrophotometer [10]. 

Particle Size: Particle size and zeta potential of the optimized 

lycopene phytosomes were done using Malvern Particle Size 

and Zeta Analyzer (Malvern Panalytical version 7.13) [11]. 

In-Vitro Release Studies: The drug release study was carried 

out using USP type II paddle type apparatus at 37 ± 0.5ºC and 

at 50 rpm using 900 ml of 0.1 N HCl (pH 1.2). Lycopene 

Suspension equivalent to 10 mg of lycopene was used for the 

test. Sample solution (5 ml) was withdrawn at predetermined 

time intervals, filtered through a 0.45 μm membrane filter, 

diluted and suitably analyzed by UV spectrophotometric 

JASCO at 471 nm. Fresh dissolution medium was replaced 

immediately after withdrawal of the test sample to maintain 

sink condition. The dissolution studies were carried out for a 

period of 2 h. and further dissolution medium pH was raised 

to 6.8 and dissolution studies was carried out for 10 h [12]. 

Anti-Oxidant Activity by DPPH Method: DPPH solution, 

1mmol/L, was prepared by dissolving 31.54 mg of DPPH in 

95% v/v buffered methanol (40mL of 0.1 mol/L acetate buffer 



Chandur & Shabaraya A                                                  Containing Lycopene Phytosomes for Improved Absorption 

 

Vol 2 | Issue 2 | Apr – Jun 2023                                                                                     Indian J Pharm Drug Studies | 84 

pH 5.5 with 60 mL of methanol) and made up to 50 ml with 

buffered methanol. The different concentrations of Lycopene 

and lycopene phytosomes such as 0.5 mg, 1 mg, 2mg, 4mg 

and 8 mg. were made up to 4 ml with distilled water. 1 ml of 

DPPH (1mmol, 3.953x10-10 μg/ml) was added to each test 

tube, shaken and the mixture was kept at 300C for 30 min. The 

471 nm is a measuring absorbance of the resulting solution. 

The effect of ascorbic acid (Vitamin C) on DPPH was also 

assessed for comparison with that of lycopene phytosomes. A 

buffered methanolic dilution (0.2, 0.4, 0.6, 0.8, 1.0 ml) of 1 

mg/ml ascorbic acid was made to 4 ml with distilled water. 1 

ml DPPH radical (1nmom/L) was added to each test tube and 

same procedure as in DPPH scavenging experiment was 

followed. The absorbance measured for the control solution 

(Buffered methanol with DPPH) was in the range 0.500 ± 

0.040. Antiradical activity was expressed as inhibition 

percentage (1%) and calculated using the following equation: 

Inhibition percentage = [(Abs control – Abs sample)/ Abs 

control] x 100 [13].  

Stability Studies: In order to determine the change in 

evaluation parameters like physical appearance, drug content, 

in vitro drug release profile on storage, stability studies of 

optimized batch was carried out at accelerated storage 

conditions at temperature 40±2˚C and 75±5% RH in a 

humidity chamber (ROTEK) as per ICH Q1C guidelines for 6 

months. Sample were withdrawn after each month and 

evaluated for changes in physical appearance, drug content 

and in vitro drug release profile [11].  

 
Fig 2: Viscosity of Liquid Orals. 

RESULTS AND DISCUSSION 

Satisfactory attempt to formulate phytosomal Oral suspension 

dosage form for controlled delivery of Lycopene using 

polymer like sodium CMC and HPMC K4M showed 

reproducible results of the executed experiments, it can be 

concluded that: The lycopene phytosomal Liquid Oral 

Suspension dosage form can be prepared by best use of 

suspending agents like sodium CMC and HPMC K4M. The 

prepared Liquid Orals were evaluated and showed to be 

uniform and stable in terms of pH of the liquid oral 

formulations was found to be in acceptable range for gastric 

absorption (pH 4.5); best to be absorbed by oral route, 

Viscosity of Liquid oral dosage forms were found to be 

satisfactory and shows the ease of pour ability from the 

container. Different concentration of suspending agents 

showed noticeable change in viscosity. Sodium CMC showed 

better suspending property than HPMC K4M. Specific gravity 

found to be near to one which is essential for a stable 

suspension and uniformity in the drug content as given in 

Table 2. 

Particle size and Zeta potential: Particle Size (450.5nm to 

467.1nm), Zeta Potential (- 21.7 to – 23.2) and Poly dispersity 

index (0.515 to 0.591) of all the respective suspension dosage 

form were up to the acceptable values for the stable 

suspension. Table 3 and Fig 3. 

Table 2: pH, Viscosity and Specific Gravity of Lycopene 

Suspension 

Code pH Viscosity 100 rpm Specific 

Gravity 

Drug 

Content % 

  cp % Torque   

LPS1 4.4 29.5 12.6 1.1058 98.8 

LPS2 4.5 42.2 18.0 1.1062 97.8 

LPS3 4.9 15.2 10.2 1.1042 96.5 

LPS4 5.1 22.3 11.6 1.1052 97.2 

Table 3: Particle Size and Zeta potential of Lycopene 

Suspension. 

Code Avg. 

Particle 

Size (nm) 

Zeta 

Potential 

Poly 

Dispersity 

Index (PDI) 

Product 

Quality 

LPS1 464.8  - 21.7 0.515 Good 

LPS2 450.5 - 21.9 0.578 Good 

LPS3 467.1 - 23.2 0.521 Good 

LPS4 594.4 - 0.591 Good 

 

Fig 3: Particle Size distribution of Lycopene Phytosome 

LPS3 



Chandur & Shabaraya A                                                  Containing Lycopene Phytosomes for Improved Absorption 

 

Vol 2 | Issue 2 | Apr – Jun 2023                                                                                     Indian J Pharm Drug Studies | 85 

Anti- Oxidant Activity: The antioxidant activity of the 

lycopene and phytosomal complex was compared taking 

ascorbic acid as standard; the results are given in Fig 4. Anti-

Oxidant activity of the extracted lycopene and Lycopene 

Phytosomal complex was performed and it found to be for 

lycopene 8 to 60 % antioxidant activity with increase in 

concentration to that of Lycopene phytosomal complex 

between 9 to 61 % compared to the standard antioxidant 

ascorbic acid. The anti-oxidant activity was found 

comparatively same for plain and complexes of lycopene, 

difference was found for duration of antioxidant activity 

which can be correlated with in-vitro dissolution studies. 

 

Fig 4: Anti-Oxidant Activity by DPPH method of Tomato 

extract and Phytosomes containing Lycopene. 

In-vitro Drug Release Studies: The percentage release of the 

drug during dissolution studies showed less than 14% release 

in first 2 hours in the acidic pH and more than 95% of release 

within 10 hours of all the formulations in pH 6.8 for LPS2 

containing 10 ml of 1% sodium CMC for 12 hours compared 

to HPMC K4M which sustained up to 10 hours.Fig 5.  

 
Fig 5: Dissolution studies of Lycopene Suspensions 

Stability Studies: Stability studies conducted for Suspension 

was found to be stable throughout the period stating that 

formulations are stable. By enhancing its therapeutic 

usefulness, phytosomes demonstrated potential technology for 

maintaining the stability of the components that are light-

sensitive. Alternative dosage forms are advised because liquid 

dosage forms choose to shorten their shelf life. 

Table 4: Stability Studies of best formulations LPS2 

Code 

LPS2 

At 25±2o C / 65±5% RH* and At 40±2o C / 

75±5% RH** for 6 months 

Month pH Viscosity %CDR at the 

end of 12 h 

Remark 

1 4.50* 42.23* 98.06* Stable 

4.60** 41.23** 98.01** Stable 

2 4.50* 42.20* 98.00* Stable 

4.65** 41.00** 98.00** Stable 

3 4.50* 42.23* 98.00* Stable 

4.60** 41.20** 98.00** Stable 

4 4.60* 42.40* 96.58* Stable 

4.60** 41.21** 96.40** Stable 

5 4.60* 42.31* 96.21* Stable 

4.65** 42.00** 96.11** Stable 

6 4.65* 42.24* 95.86* Stable 

4.60*8 41.23** 95.12** Stable 

CONCLUSION 

For the reproducible outcomes of the carried out studies, a 

satisfactory attempt has been made to manufacture 

phytosomal Oral suspension dosage forms for controlled 

delivery of lycopene utilising 10 mL of 1% polymers like 

sodium CMC and HPMC K4M. In order to include stable 

goods into oral liquid dosage forms, lycopene complexes with 

phospholipids were successfully created into phytosomes. 

This was a good innovation in the field of nanotechnology. 

The pH, specific gravity, particle size, and zeta potential of an 

elegant suspension, among other characteristics, were all 

found to be within acceptable limits. Compared to the 

commercially available traditional dosage form, the 

therapeutic concentration of the food component could be 

sustained for a period of 12 hours (Syrup).  

Acknowledgement: Authors are thankful to Vision Group of 

Science and Technology, Govt. of Karnataka, and Srinivas 

College of Pharmacy Mangalore for providing laboratory 

facilities to carry out the research work. 

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100

%
 In

h
ib

it
io

n

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Chandur & Shabaraya A                                                  Containing Lycopene Phytosomes for Improved Absorption 

 

Vol 2 | Issue 2 | Apr – Jun 2023                                                                                     Indian J Pharm Drug Studies | 86 

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How to cite this article: Viresh K Chandur, Ramkrishna 

Shabaraya A. Characterization of Liquid Oral Containing 

Lycopene Phytosomes for Improved Absorption. Indian J 

Pharm Drug Studies. 2023: 2(2) 82-86. 

Funding: None                  Conflict of Interest: None Stated 

 


