Journal of Pharmacy And Bioallied Sciences

: 2019  |  Volume : 11  |  Issue : 8  |  Page : 547--550

Physical study of Chloramphenicol In Situ Gel with Base Hydroxypropyl Methylcellulose and Poloxamer 188

Insan S Kurniawansyah, Dolih Gozali, Iyan Sopyan, Muhammad Iqbal, Anas Subarnas 
 Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia

Correspondence Address:
Insan S Kurniawansyah
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang.


Objective: The aim of this study was to determine the best formulation of ophthalmic in situ gel preparation by two different bases, Poloxamer 188 and HPMC (hydroxypropyl methylcellulose), with physical evaluation, such as organoleptic, pH, viscosity, and gel capacity during 28 days of storage time. Materials and Methods: The two different concentrations of the gel made by using Poloxamer 188 were F1 (5%) and F2 (10%), and those made by using HPMC were F3 (0.45%) and F4 (1%). Results: The results of this study showed that formulation 1 (F1) was the optimum formulation, having pH 6.45, viscosity of 5.47 cP, and a better gel capacity than other formulas. Conclusion: In situ gel for ophthalmic preparations is developed to mask the limitation of conventional forms of ophthalmic preparation. In situ gel technology significantly increase the effectivity of drugs in the raw material and drug bioavailability in new drug delivery systems based on in situ gel concept.

How to cite this article:
Kurniawansyah IS, Gozali D, Sopyan I, Iqbal M, Subarnas A. Physical study of Chloramphenicol In Situ Gel with Base Hydroxypropyl Methylcellulose and Poloxamer 188.J Pharm Bioall Sci 2019;11:547-550

How to cite this URL:
Kurniawansyah IS, Gozali D, Sopyan I, Iqbal M, Subarnas A. Physical study of Chloramphenicol In Situ Gel with Base Hydroxypropyl Methylcellulose and Poloxamer 188. J Pharm Bioall Sci [serial online] 2019 [cited 2022 Jun 25 ];11:547-550
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The conventional ophthalmic preparation is washed out from the precorneal area on instillation because of constant lacrimal secretion, nasolacrimal drainage, and short precorneal residence time of the solution.[1],[2],[3] The different ophthalmic preparations such as viscous solutions, ointments, gels, suspensions, or polymeric inserts are used to increase precorneal residence time and ocular bioavailability, but because of blurred vision (e.g., ointments) or lack of patient compliance (e.g., inserts), these ocular drug delivery systems have not been used extensively until now.[2],[4]

An alternative approach to increase drug availability (retention time) in precornea and bioavailability can be achieved using a new drug delivery system based on the concept of in situ gel formation.[5]In situ gelling system is described as a liquid dosage, which change into gel form in a suitable condition.[6]In situ gel system has advantages such as its ability to reproduce and administer drugs more accurately and not cause many problems with vision unlike the previously formed eye drop formulations.[7]

Many polymers are very useful, which undergo reversible sol to gel phase transition in response to physiological stimuli. The sol–gel transition occurs as a result of a chemical or physical condition, which is induced by physiological environment.[8] Poloxamer, a thermoresponsive polymer, exists in a liquid state at low temperature, that is, between 4° and 5°C at a concentration range of 20%–30% wt/wt, while converting into a gel on increasing the temperature of the medium. It has been widely used in nasal,[9] ophthalmic,[10] vaginal,[11] and topical[12] formulations. However, one of the limitations of Poloxamer is its weak mechanical strength, leading to a rapid erosion of the polymer. Furthermore, it was previously reported that Poloxamer, at a concentration of 18% (wt/vol) or higher, has the ability to transform from a low-viscosity solution into a gel under the ambient temperature. However, at this concentration, the solution will lose its gelation ability after being diluted by lacrimal fluid on instillation into the eye. Hence, 25% (wt/wt) Poloxamer can be used to ensure the completion of the phase transition process of the polymer under ocular physiological condition. However, under these circumstances, the gelation temperature will be lower than the room temperature, and Poloxamer solution will have to be stored in the refrigerator, which makes it inconvenient for use. Moreover, previous reports have revealed that higher concentrations of Poloxamer are required in a formulation when used on its own; such concentrations were found to be irritant to the eye. To overcome this challenge, researchers adopted the approach of blending Poloxamer with other polymers such as methyl cellulose, chitosan, and others to decrease the total concentration of Poloxamer used, to improve its gelling characteristics as well as mechanical properties of Poloxamer, and to reduce its ocular irritation potential.[13]

The aim of this study was to formulate thermosensitive in situ gel for ocular delivery systems. The model of the drug used was chloramphenicol, one of the broad-spectrum antibiotics against gram-positive, gram-negative, and anaerobic bacteria. Chloramphenicol intraocular penetration is very good because of its high lipid solubility.[8],[14]

 Materials and Methods


Chloramphenicol (Bio Basic Markham, Ontario, Canada), hydroxypropyl methylcellulose (HPMC) (Colorcon, USA), Poloxamer 188 (Kolliphor P 188; BASF, Indonesia), propylene glycol, potassium dihydrogen phosphate (Merck; New Jersey USA), sodium hydroxide (Merck), ethanol, and aqua bidest sterile (Ikhaparmindo, Indonesia) were used in this study.


Different formulations were prepared with various concentrations of HPMC and Poloxamer 188 as described in [Table 1]. The drug that soluble in propylene glycol was added into the base of in situ gel while and stirrer continuously to avoid foam formation. The buffer solution was added into the formulation, and followed by addition of distilled water up to 100mL. Furthermore, the formulations were stored in 10-mL closed vials. This formulation was terminally sterilized by autoclaving at 121°C for 15min.[15]{Table 1}

Determination of visual appearance, clarity, and pH

Visual appearance was determined by various ways, the first method was to observe the product under fluorescent light with black and white as the background in a cabinet, which has sufficient light. The second method was measuring pH with pH meter. The pH meter must be calibrated before use with buffered solution at pH 4 and 7. The pH was measured for the storage time at 0, 1, 3, 5, 7, 14, 21, and 28 days. The last parameter was gelling capacity of formulations, which was evaluated to determine in situ gel ability of the formulations. Gelling capacity was determined by mixing the formulation with simulated tear fluid in the proportion 25:7 and was examined visually.[16],[17],[18],[19] The visual parameters of gelling capacity are listed in [Table 2].{Table 2}


The ophthalmic in situ gel of chloramphenicol was prepared by dissolution technique under aseptic condition and was characterized on the physical characteristics such as visual appearance, clarity, pH, viscosity, and gelling capacity based on the observation result during storage time for 28 days. The physical characteristics of different formulations are shown in [Table 3].{Table 3}

There was an increase and decrease in pH during the 28-day storage period [Figure 1].{Figure 1}

The study of gelling capacity showed that F1 (5% Poloxamer 188) and F4 (1% HPMC) had a better gelling capacity compared to F2 (10% Poloxamer 188) and F3 (0.45% HPMC). The statistical analysis showed that the initial hypothesis determined in this study was H0 has no significant difference given by Poloxamer 188 and HPMC to the first untill fourth formulas. The second hypothesis was H1, which was opposite of H0. On the basis of analysis of variance (ANOVA), results for pH showed that F1 had an F value of 32.792 and a P value less than 0.05. F2 had an F value of 0.848 and a P value of more than 0.05. F3 had an F value of 17.875 and a P value less than 0.05. F4 had an F value of 7.026 and a P value of less than 0.05. ANOVA results for viscosity showed that F1 had an F value of 5.619 and a P value less than 0.05. F2 had an F value of 1.555 and a P value of more than 0.05. F3 had an F value of 1061.267 and a P value less than 0.05. F4 had an F value of 986.573 and a P value of less than 0.05. On the basis of the results of ANOVA, F1, F3, and F4 did not show a significant change in pH value and viscosity during storage time, whereas F2 showed a significant change in pH and viscosity during storage time.


Ophthalmic formulation produced must be stable and clear.[15] It can be seen from [Table 3], that all formulation produce visual appearance for 28 storage days that met the requirements of 5th edition Indonesian Pharmacopoeia.[20]

There was an increase and a decrease in pH value during the 28-day storage period [Figure 1], F1 and F2 with the Poloxamer 188 base remained within the pH range of 5–7.4.[21] F3 and F4 that used HPMC base showed a decrease in pH, that is, below the pH value of 5, which was below the specified in situ gel pH range. A pH value below 5.5 can cause the chloramphenicol substances in in situ gel preparations to become unstable because the pH stability of chloramphenicol preparation is between 5.5 and 7.4.[8],[21]

The results of viscosity of F1–F4 gave results, which meet the requirement in the literature. The viscosity produced by in situ gel preparations must be in the range of 5–100 cP.[22] The HPMC molecule contains methoxy group, which reduces the critical temperature to increase the viscosity. Higher concentration of HPMC used will increase the viscosity of the preparation.

The study of gelling capacity showed that F1 (5% Poloxamer 188) and F4 (1% HPMC) had a better gel capacity value compared to F2 (10% Poloxamer 188) and F3 (0.45% HPMC). Poloxamer 188 has an amphiphilic structure that can increase the solubility of an insoluble substance in water by increasing the mixing (miscibility) between two incompatible substances.[23] The term of “poloxamer” generally named with the “P’ letter (for Poloxamer) followed by three digits: the first two digits multiplied by 100 give the approximate molecular mass of polyoxypropylene, and the last digit multiplied by 10 gives the percentage of polyoxyethylene content (for example P188 = Poloxamer with polyoxypropylene molecular mass of 1800g/mol and 80% polyoxyethylene content.[24] F2 has a higher Poloxamer 188 base concentration compared to F1; when instilled into an artificial tear solution at 35°C, the gel formed faster than F1.

HPMC can form colloids when dissolved in water through its ability to clot and absorb water. It is a water-containing (aqueous) substance that shows the nature of gelation when heated to a critical temperature. The HPMC solution becomes viscous and forms a mass that cannot flow but is semiflexible.[25] The critical temperature for HPMC is inversely proportional to the concentration of HPMC used. The higher the HPMC concentration used, the lower the critical temperature for the HPMC solution to become viscous. F4 preparation had a better geliing capacity than F3, because F4 has a higher HPMC. So the F4 in situ gel was formed faster when its inserted to artificial tears and longer to melt compared F3.


On the basis of the measurement of physical characteristic, it was concluded that formula 1 with 5% Poloxamer 188 as a base is the best formula for in situ gel preparation.

Financial support and sponsorship

This work was supported by DRPMI Universitas Padjadjaran, Sumedang, Indonesia.

Conflicts of interest

There are no conflicts of interest.


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