Home  |  About JAPTR |  Editorial board  |  Search |  Ahead of print  |  Current issue  |  Archives |  Submit article  |  Instructions  |  Subscribe  |  Advertise  |  Contacts  |Login 
Users Online: 1003   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
     

 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 13  |  Issue : 4  |  Page : 306-311  

Preparation and evaluation of oral soft chewable jelly containing flurbiprofen


Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq

Date of Submission28-Jun-2022
Date of Decision08-Jul-2022
Date of Acceptance09-Jul-2022
Date of Web Publication10-Oct-2022

Correspondence Address:
Dr. Lubna Abdalkarim Sabri
Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad
Iraq
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/japtr.japtr_465_22

Rights and Permissions
  Abstract 


Oral jelly is a semisolid preparation that could resolve problem associated with dosage form's swallowing, especially in pediatric and elderly ones. This work aimed to prepare oral flurbiprofen (FBP) jelly to improve patient compliance. Heating and congealing method was used to prepare FBP jelly using three different polymers (pectin, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose). The effect of different concentrations of pectin and sucrose on jelly properties was studied. The results revealed that both pectin and sodium carboxymethyl cellulose polymers gave acceptable jelly appearance and consistency. It was also observed that the increase of pectin or sucrose concentration had a significant impact on jelly viscosity. All pectin jellies except formula containing 5.5% pectin and 50% weight by volume (w/v) sucrose exhibited more than 50% and 85% of FBP releasing within 15 and 30 min, respectively. The formula (FP2) consisting of 4.5% pectin and 40% w/v sucrose was selected as optimum formula which had a high percent dissolution efficiency (78.95%) and better consistency during handling. This work succeeded in the preparation of new FBP oral jelly, which can be considered a promising dosage form for enhancement of patient compliance and drug solubility.

Keywords: Dysphagia, easily swallowing, flurbiprofen, oral jelly, pectin


How to cite this article:
Sabri LA, Khasraghi AH, Sulaiman HT. Preparation and evaluation of oral soft chewable jelly containing flurbiprofen. J Adv Pharm Technol Res 2022;13:306-11

How to cite this URL:
Sabri LA, Khasraghi AH, Sulaiman HT. Preparation and evaluation of oral soft chewable jelly containing flurbiprofen. J Adv Pharm Technol Res [serial online] 2022 [cited 2022 Nov 28];13:306-11. Available from: https://www.japtr.org/text.asp?2022/13/4/306/358221




  Introduction Top


The oral route is the most common route of drug administration. Till today, it is still a widely preferred and acceptable route among patients owing to its advantages, such as ease of administration, safeness, noninvasiveness, and convenience for self-administration.[1]

However, one of the obstacles to oral drug delivery experienced by many patients, particularly pediatric and geriatric population, is dysphagia. Dysphagia causes difficulties in swallowing conventional solid oral medicines and the risk of choking by liquid preparations. Consequently, patients usually try to crush hard tablets or open capsules and mix them with food or water to become swallowing easily. Such behavior can result in dosing inaccuracy and changing of drug release and absorption, as well as undesirable drug taste palatability.[2],[3]

Today, one of the appropriate potential alternative oral dosage forms is jelly, similar to gelatinous food and confection. The jellies can address swallowing problems, ensure patient safety, and ease of handle and taken without water. Thus, jellies can improve patient compliance in addition to their flavoring taste and esthetic pleasant appearance. Jellies have advantages of both solid and liquid preparations.[4]

Jellies intended for oral administration mean “nonflowable gelatinous preparations of definite size and shape” and must meet the requirements of dissolution and content uniformity according to the Japanese pharmacopeia.[5] Recently, several drugs have been marketed as medicated oral jelly, such as tadalafil (Apcalis®, Ajanta), alendronate (Bonalon®, Teijin Pharma Limited), and donepezil (Aricept®, Eisai). In addition, numerous research studies to improve patient acceptance and/or enhance drug bioavailability have been published.[6],[7]

The main excipients of jellies are a gelling agent, stabilizer, preservative, and flavoring and sweetening agents. Jellies act as a vehicle for a drug which presents either as dissolved or dispersed/suspended form that can release and mix with saliva to be absorbed through gastrointestinal tract mucosa. By choosing the right gelling agent, which can be either natural or synthetic hydrophilic polymers at a suitable concentration, the drug can release immediately or sustained from the jelly vehicle.[8]

Flurbiprofen (FBP) is one of the widely used nonsteroidal anti-inflammatory drugs. FBP acts as a potent pain reliever. Recent reports suggest its potential topical and systemic use in the inhibition of colon tumor and platelet aggregation.[9] FBP is also considered a promising medicine for the management of Alzheimer's disease.[10] However, Food and Drug Administration (FDA) approval oral formulations of FBP are only as tablets of different strengths and capsules.

The objective of this study was to prepare an oral FBP jelly to be easily swallowed by geriatric and pediatric patients. To achieve our aim, the effect of three gelling agents; pectin, hydroxypropyl methylcellulose K100 (HPMC K100), and sodium carboxymethyl cellulose (SodCMC), on physicochemical properties include appearance, texture, and in vitro release profile of the prepared jellies were evaluated to select the optimum formula.


  Materials and Methods Top


FBP and HPMC K100 were purchased from (Hangzhou Hyper Chemicals Limited, Zhejiang, China). Pectin was purchased from (Cargill,Redon, France), SodCMC, and Tween 80 were from (Alpha Chemika,India). Polyethylene glycol (PEG400) was from (J.T Baker, China). Citric acid, methylparaben, and propylparaben were purchased from (Fluka Chemical AG, Switzerland).

Methods

Preformulation studies

The drug–polymer compatibility study was carried out after incubation of the pure drug and a 1:1 ratio physical mixture of FBP and each gelling agent in the oven at 40°C for 2 weeks by comparing Fourier-transform infrared (FTIR) spectra (4000-400 cm− 1) using (FTIR-Shimadzu, Japan).[11]

Preparation of flurbiprofen jelly

Several jelly formulations were prepared using heating and congealing method.[12] Three gelling agents (pectin, HPMC K100, and SodCMC) were used [Table 1]. Each of the polymers was dispersed in a small volume of warm distilled water and stirred using a magnetic stirrer to facilitate the hydration of hydrophilic polymer. Then, the required amount of sucrose will add to the polymer solution with continuous stirring; after that, FBP and all the remaining excipients are added under stirring. The final weight was adjusted to 25 g with distilled water. Then was poured into molds to be stored as separate unit doses (the weight of each dose is 2.5 g and contains 50 mg FBP) and allowed to cold at room temperature.
Table 1: The components of different formulations of oral flurbiprofen jelly

Click here to view


Characterization of flurbiprofen jelly

Determination of physical appearance and pH

All prepared FBP jellies were inspected visually for appearances such as color, transparency, homogeneity, and consistency. Grittiness and stickiness were evaluated by mild rubbing of the prepared jellies between the thumb and index fingers.[13] One gram of each prepared FBP jelly was weighed and dispersed in 100 mL of distilled water and pH was examined.

Weight variation, drug content uniformity, and syneresis

For each formulation, ten jellies were taken and their individual weight was determined. The average weight percent was calculated. Furthermore, three jelly units of each formulation were taken in a separate volumetric flask. The phosphate buffer (pH 7.2) was added and continuously stirred to dissolve FBP. Then, the solution was filtered and diluted suitably to analyze at 247 nm by ultraviolet spectrophotometer.[14] Syneresis was performed by visual inspection for any change in jelly consistency or size shrinkage after 48 h storage at room temperature. Hence, jellies that undergo syneresis would be excluded from further evaluation tests.[15]

Viscosity

The viscosity of jellies was measured using (VR 3000 MYR Viscometers) with spindle number 7 at 25°C. Viscosity spindle was inserted in 50 g of prepared sample and rotated at speeds that were 10 rpm.[13]

Texture analysis

The textural description of jelly, as its mouthfeel in terms of firmness, was determined using the (TA. XT Plus-Stable Micro Systems) texture analyzer. Using compression analysis, the texture profile analysis was performed using probe P100 and set with a trigger of 5 g, deformation of 1.2 mm, and a speed of 1.0 mm/s. The maximum force value on the graph is a measure of firmness.[16]

In vitro flurbiprofen dissolution

The dissolution test was carried out using the paddle method (apparatus II with a stirring rate of 50 rpm at 37°C and phosphate buffer medium pH 7.2). A volume of 5 mL of the dissolution medium was taken at the time points of 5, 10, 15, 20, 30, 45, and 60 min, filtered, diluted, and analyzed at λmax 247 as listed in the USP Pharmacopeia 11th edition. The drug release performances of prepared jellies have been compared using cumulative percent release at 15 min, the dissolution efficiency (% DE), and mean dissolution time (MDT) at the end of 60 min. For quantitative kinetic analysis of FBP release profile from optimum jelly formulation, DDSolver software was applied to investigate the best data fit to order.[17]

Statistical analysis

All experiments were done in triplicate for each sample; the results were presented as mean ± standard deviation. One-way analysis of variance analysis was employed to identify significant differences between data. Data were analyzed by omitting the insignificant term with probability value (P) ≤0.05.


  Results and Discussion Top


Preformulation studies

The FTIR spectral of FBP powder showed two characteristic peaks; carbonyl stretching band donated at 1696.02 cm− 1 and broad peak of O-H stretching of the carboxylic acid group at 2500–3300 cm− 1 were investigated. The other characteristic peak was C-F stretching at 1217.83 cm− 1 [Figure 1]a. The results were inconsistent with Sohail et al. findings.[18] For the physical mixture of drug and polymer, there is no significant deviation in three characteristic FBP peaks [Figure 1b-d], meaning that there was no considerable impact of polymer existence on the integrity of FBP peaks and confirmed compatibility.
Figure 1: FTIR spectrum of (a) pure flurbiprofen, the physical mixture of flurbiprofen with (b) HPMC K100, (c) SodCMC, and (d) pectin. FTIR: Fourier-transform infrared

Click here to view


Preparation of flurbiprofen jelly

Based on the earlier study, PEG400 and Tween 80 were used as cosolvent and surfactant, respectively, to enhance FBP solubility based on published studies.[14],[19] Sucrose is selected as sweeteners to improve the taste and viscosity of the formulation.

PEG 400 at a concentration higher than 3% weight by volume (w/v) was found to affect the consistency of jellies. Increasing the concentration of HPMC and SodCMC above 3.5% w/v resulted in a very viscous gel that was difficult to be poured into molds.

Characterization of flurbiprofen jelly

All prepared FBP jellies had a pleasant odor with bright yellow color for pectin formulations (FP1-FP5), whereas SodCMC formula had white color as shown in [Figure 2]. [Table 2] summarizes the appearance parameters. All formulations showed good homogeneity without significant stickiness during holding except the formula (FHP1) containing HPMC K100. Hence, the formula FHP1 was excluded from further tests.
Figure 2: The appearance color of SodCMC formula FSC1 (middle) and pectin formulas (FP1 – left and FP2 – right)

Click here to view
Table 2: The result parameters of the physical appearance of flurbiprofen oral jelly

Click here to view


The pH value of oral jelly formulations as shown in [Table 3] was found to be in the range of 3.58–4.19. This is considered to be slightly acidic due to citric acid incorporation as pH modifier to enhance the gelling ability of pectin and stabilize it.[5] Pectin is a natural polysaccharide with a negatively charged carboxylic group of galacturonic acid units which interfere with pectin gelation. When the pH increased, pectin gelation decreased as a result of higher charge density with higher electrostatic repulsion among the pectin molecules, thus preventing the cross-linking and formation of a three-dimension triple helix network.[20] While at the pH range of 3.5–4.2, hydrophobic interactions formed between methyl ester groups and hydrogen bonding occurred between undissociated carboxyl groups, leading to form elastic and stable gel.[21]
Table 3: The results of evaluated parameters for flurbiprofen oral jelly formulations

Click here to view


The weight variations of all prepared formulas were ranged between 2.75% ± 0.161% and 3.78% ± 0.207% [Table 3]. The jelly content of FBP in the tested formulations was within the acceptable pharmacopeia limit and ranged between 97.950 and 99.58%; there was no statistically significant difference, indicating the uniform distribution of FBF.

All formulations contain pectin as the gelling agent did not show any syneresis due to immobilization of free water by sucrose at prepared pH.[22] Meanwhile, the formula (FSC1) showed syneresis, so it was excluded from further evaluation.

The viscosity of the evaluated jellies was illustrated in [Table 3]. The increase in percent w/v of pectin would significantly (P ≤ 0.05) increase viscosity. These results are attributed to improve intermolecular interactions between pectin molecules and reduce intermolecular distance.[23] From this data, it was suggested that pectin concentration directly influenced the gel strength and viscosity, a similar finding was reported by Prakash.[13]

In addition, it was observed that at constant pectin concentration, the increase in sucrose concentration had a significant impact on jelly viscosity due to sucrose would stabilize the junction zone through the addition of more hydrogen bonding during pectin gelation, so increase gel strength.[21],[23]

Texture properties play an important role in swallowing physiology and hence consumer palatability and acceptance. Soft jelly, which has a low firmness value, is more chewable and easily swallowed with a low risk of aspiration.[24] Data demonstrated that both pectin polymer and sucrose had a significant (P ≤ 0.05) effect on the firmness. It was observed when increasing pectin concentrations from 3.5% to 4.5% and 5.5 w/v percent, the firmness increased from 153.8 ± 13.9 to 188.65 ± 10.38 and 391.01 ± 30.7 g, respectively. In addition, there was a direct correlation observed between sucrose concentration and firmness at constant pectin.

In vitro flurbiprofen dissolution

As illustrated in [Figure 3], increasing pectin percent from 3.5% to 4.5% w/v percent had a nonsignificant (P > 0.05) impact on FBP releasing during the first 30 min. On the contrary, FBP percent released had revealed a significant (P ≤ 0.05) decrease with an increase in pectin content up to 5.5% w/v. On the other hand, at a constant pectin percent of 4.5% w/v, there was a significant decrease in FBP percent released with increasing sucrose percentage [Figure 4]. This can be explained by the influence of the interstices fluid viscosity of jelly matrix on the dissolution rate which it decreased with increasing polymer or sucrose concentration.[25]
Figure 3: Comparative flurbiprofen dissolution profile from prepared jellies at different pectin concentrations

Click here to view
Figure 4: Comparative flurbiprofen dissolution profile from prepared jellies at constant pectin concentration (4.5% w/v) with different sucrose concentration

Click here to view


Regardless of the difference in the percent of the components between the prepared formulations, all pectin jellies except formula FP5 showed more than 50% and 85% of FBP released within the first 15 and 30 min, respectively [Table 4]. These dissolution results were satisfying with immediate release dosage requirements; such fast dissolution may be explained by hydrophilic pectin nature which has the ability to easily disintegrate and dissolve in a basic medium and hence causes faster drug release.[26]
Table 4: The dissolution parameters of flurbiprofen oral jelly

Click here to view


[Table 4] shows the lowest MDT60 min and highest percent DE values indicated faster FBP released from jelly formulations. Although the formula (FP4) showed the highest percent DE and lowest MDT60 min, the formula FP2 was selected as optimum formula which also had a high percent DE (78.95%) and better consistency and handling compared to formula FP4.

The results of FBP release kinetics from formula (FP2) revealed that a higher coefficient of determination value (R2 = 0.9784) was for first-order kinetic [Table 5]. While the fitting of the drug released data on Korsmeyer–Peppas model showed nonfickain mechanism of drug transport (n value between 0.5 and 1) that assumed the drug releasing depends on both diffusion and polymer swelling with the time.[17]
Table 5: The determination coefficients of different mathematical models of formula FP2

Click here to view



  Conculsion Top


One of the strategies for enhancing oral FBP solid dosage acceptance by pediatric, geriatric, and patients with swallowing difficulties is to formulate the drug as soft jelly. Both type and concentration of polymer had an impact on jelly consistency. Increasing pectin concentration would increase jelly viscosity and hardness. The formula (FP2) consisting of 4.5% pectin and 40% w/v sucrose was selected as optimum formula which had a high percent DE (78.95%) and better consistency during handling with acceptable jelly characteristics.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hua S. Advances in oral drug delivery for regional targeting in the gastrointestinal tract-Influence of physiological, pathophysiological and pharmaceutical factors. Front Pharmacol 2020;11:524.  Back to cited text no. 1
    
2.
Hosseini A, Bagheri F, Mohammadi G, Azami M, Tahvilan R. Design and preparation of oral jelly candies of acetaminophen and its nanoparticles. Appl Nanosci 2022;12:101-7.  Back to cited text no. 2
    
3.
Dille MJ, Hattrem MN, Draget KI. Soft, chewable gelatin-based pharmaceutical oral formulations: A technical approach. Pharm Dev Technol 2018;23:504-11.  Back to cited text no. 3
    
4.
Gomaa E, Ayoub MM. Vardenafil oral jellies as a potential approach for management of pediatric irritable bowel syndrome. Saudi Pharm J 2021;29:955-62.  Back to cited text no. 4
    
5.
Sunil S, Sharma UK, Arathy SA. Pharmaceutical Jellies: A novel way of drug delivery. J Pharm Sci Res 2020;12:904-9.  Back to cited text no. 5
    
6.
Mahdin ZH. Oral jellies for improving oral drug delivery in dysphagia. Al Mustansiriyah J Pharm Sci 2020;20:94-104.  Back to cited text no. 6
    
7.
Kim KH, Jun M, Lee MK. Bioavailability of the common cold medicines in jellies for oral administration. Pharmaceutics 2020;12:1073.  Back to cited text no. 7
    
8.
Kaur G, Gananarajan G. A Review article on oral jellies for pediatrics. Indo Am J Pharm Sci 2018;5:444-52.  Back to cited text no. 8
    
9.
Kadhim ZM, Mahmood HS, Alaayedi M, Ghareeb MM. Formulation of flurbiprofen as microsponge drug delivery system. Int J Pharm Res 2020;12:748-53.  Back to cited text no. 9
    
10.
Surov AO, Manin AN, Voronin AP, Boycov DE, Magdysyuk OV, Perlovich GL. New pharmaceutical cocrystal forms of furbiprofen: Structural, physicochemical, and thermodynamic characterization. Cryst Growth Des 2019;19:5751-61.  Back to cited text no. 10
    
11.
Hussien RM, Ghareeb MM. Formulation and characterization of isradipine nanoparticle for dissolution enhancement. Iraqi J Pharm Sci 2021;30:218-25.  Back to cited text no. 11
    
12.
Gohel MC, Parikh RK, Nagori SA, Shah SN, Dabhi MR. Preparation and evaluation of soft gellan gum gel containing paracetamol. Indian J Pharm Sci 2009;71:120-4.  Back to cited text no. 12
[PUBMED]  [Full text]  
13.
Prakash K, Satyanarayana VM, Nagiat HT, Fathi AH, Shanta AK, Prameela AR. Formulation development and evaluation of novel oral jellies of carbamazepine using pectin, guar gum, and gellan gum. Asian J Pharm 2014;8:241-17.  Back to cited text no. 13
  [Full text]  
14.
Abd-Alhammid SN, Saleeh HH. Formulation and evaluation of flurbiprofen oral film. Iraqi J Pharm Sci 2014;23:53-9.  Back to cited text no. 14
    
15.
Mahdi ZH, Maraie NK, Al-Juboori ZA, Najm AS. The development and characterization of a new easily swallowed valsartan oral jelly. Res J Pharm Tech 2022;15:723-816.  Back to cited text no. 15
    
16.
Čižauskaitė U, Jakubaitytė G, Žitkevičius V, Kasparavičienė G. Natural ingredients-based gummy bear composition designed according to texture analysis and sensory evaluation in vivo. Molecules 2019;24:1442.  Back to cited text no. 16
    
17.
Preethy AJ, Paarakh MP, Setty CM, Peter Chirstoper GV. Release kinetics-Concepts and applications. Int J Pharm Res Technol 2018;8:12-20.  Back to cited text no. 17
    
18.
Sohail MF, Shah PA, Tariq I, Saeedul- Hassan S, Amin U, Raza SA, et al. Development and in vitro evaluation of flurbiprofen microcapsules prepared by modified solvent evaporation technique. Trop J Pharm Res 2014;13:1031-8.  Back to cited text no. 18
    
19.
Vemula SK, Radhika K. Liquisolid compact Technique for Improvement of the dissolution rate of flurbiprofen: Formulation and evaluation. J Drug Res Dev 2015;1:1-5.  Back to cited text no. 19
    
20.
Narasimman P, Sethuraman P. An overview on the fundamentals of pectin. Int J Adv Res 2016;4:1855-60.  Back to cited text no. 20
    
21.
Han W, Meng Y, Hu C, Dong G, Qu Y, Deng H, et al. Mathematical model of Ca2+concentration, pH, pectin concentration and soluble solids (sucrose) on the gelation of low methoxyl pectin. Food Hydrocolloids 2017;66:37-48.  Back to cited text no. 21
    
22.
Mohapatra A, Parikh RK, Gohel M. Formulation, development and evaluation of patient friendly dosage forms of metformin, Part-II: Oral soft gel. Asian J Pharm 2008;2:172.  Back to cited text no. 22
  [Full text]  
23.
Gawkowska D, Cybulska J, Zdunek A. Structure-related gelling of pectins and linking with other natural compounds: A review. Polymers (Basel) 2018;10:E762.  Back to cited text no. 23
    
24.
Almurisi SH, Doolaanea AA, Akkawi ME, Chatterjee B, Ahmed Saeed Aljapairai K, Islam Sarker MZ. Formulation development of paracetamol instant jelly for pediatric use. Drug Dev Ind Pharm 2020;46:1373-83.  Back to cited text no. 24
    
25.
Hanawa T, Watanabe A, Tsuchiya T, Ikoma R, Hidaka M, Sugihara M. New oral dosage form for elderly patients. II. Release behavior of benfotiamine from silk fibroin gel. Chem Pharm Bull (Tokyo) 1995;43:872-6.  Back to cited text no. 25
    
26.
Sundar Raj AA, Rubila S, Jayabalan R, Ranganathan TV. A Review on pectin: Chemistry due to general properties of pectin and its pharmaceutical uses. Open Access Sci Rep 2012;1:1-4.  Back to cited text no. 26
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
   Abstract
  Introduction
   Materials and Me...
   Results and Disc...
  Conculsion
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed454    
    Printed14    
    Emailed0    
    PDF Downloaded63    
    Comments [Add]    

Recommend this journal