265

Drug Discoveries & Therapeutics. 2024; 18(4):265-268.

Brief Report

DOI: 10.5582/ddt.2024.01051

Differences in fluidity and viscosity of brand-name and genericinjectable ointment
Atsushi Ishimura1, Chiaki Ogawa2, Megumi Yatabe3, Kentaro Tani2, Motoki Inoue4,*
1

Division of Practical Pharmacy, Nihon Pharmaceutical University, Saitama, Japan;
Department of Pharmacy, NHO Tokyo Medical Center, Tokyo, Japan;
3
Department of Pharmacy, NHO Saitama Hospital, Saitama, Japan;
4
Department of Physical Chemistry, Hoshi University, Tokyo, Japan.
2SUMMARY

Generic medications contain the identical active ingredient in the same concentration as their branded
counterparts and are administered in the same manner, aiming to deliver comparable efficacy,
dosage, and clinical outcomes. Nevertheless, variations in additives and formulation processes,
particularly noticeable in topical medications, can influence factors like ease of use and patientadherence. Therefore, in this study, we aimed to compare the rheological attributes of branded andgeneric injectable ointments, assessing disparities in formulation performance and their impact onpatient care. Posterisan® Forte and Hemoporison® ointments were used as the branded and genericversions, respectively, and their viscosity, ductility, and viscoelastic properties were evaluated.
Posterisan® Forte showcased enhanced spread ability, maintaining uniform flow characteristics acrossvarying temperatures, whereas Hemoporison® displayed pronounced thixotropic properties andstiffness, suggesting potential benefits for applications necessitating reversible viscosity adjustments
and heightened rigidity. Despite sharing identical additives, observable differences in physicalcharacteristics highlight the necessity of understanding formulation traits, which could influenceointment behavior. Alterations in fluidity and viscosity may affect how patients perceive and apply themedication, potentially influencing treatment outcomes and the occurrence of adverse effects.

Keywords

Generic drugs, brand-name drugs, injectable ointments, rheological properties, patient treatment

1. Introduction
Generic drugs, which contain the same active ingredientin the same amount as their brand-name counterparts,
are administered via the same route, and are designed
to provide equivalent efficacy, dosage, and clinicaleffect. Because they bypass the need for extensive
drug discovery research and clinical trials (except forbioequivalence studies), generic drugs are typicallymore affordable. As such, their utilization is advocatedfor the dual purpose of reducing national healthcare
expenditures and alleviating patient financial burdens (1).
In Japan, revisions in reimbursement policies have
led to a significant expansion in the utilization of genericdrugs, with approximately 80% of drugs by sales volume
being generics as of September 2023. However, in termsof value, generics account for only 56.7% of drug usage.
This discrepancy is partly attributed to the slow adoptionof generic alternatives for expensive medications.
Moreover, differences in additives and formulation

processes between generic and brand-name drugs,
particularly in topical formulations, can impact factors
such as usability and patient adherence to treatment. For
instance, variations in properties like viscoelasticity, evenin common additives like white Vaseline, can influence
the quality and user experience of topical medications(2). Although pharmaceutical formulation guidelinesemphasize the importance of ensuring efficacy, safety,
quality, and stability, post-marketing considerations suchas supply stability and promoting proper medication
adherence are equally crucial (3,4). Regardless of a
drug's efficacy, therapeutic outcomes are contingent uponpatients adhering to correct dosage and administration
instructions. In the case of topical medications, which
are directly applied to the site of action, factors such as
texture and usability play a pivotal role. Furthermore, ininjectable ointments, the amount of medication dispensed
depends on the force applied during administration.
Elderly patients, whose physical abilities may decline,
may encounter difficulties in administering ointments

www.ddtjournal.com

266

Drug Discoveries & Therapeutics. 2024; 18(4):265-268.
effectively, impacting treatment outcomes (5).
Therefore, in this study, we aimed to compare therheological characteristics of brand-name and genericinjectable ointments to evaluate potential differencesin formulation performance and their implications
for patient treatment. Although both brand-name andgeneric injectable ointments used in this study shared
the same additives, discrepancies in physical properties
were observed. This emphasizes the importance ofunderstanding formulation characteristics, which may
affect ointment behavior.
2. Materials and Methods

Fisher Scientific K.K., Tokyo, Japan) equipped with aparallel plate PP35 (diameter 35 mm, gap 0.3 mm) tomeasure stress value (Pa), storage modulus (G') andloss modulus (G"). For rate-dependent measurements,
stress values were recorded while varying the shear ratefrom 0 to 500 s-1 and then from 500 to 0 s-1, and the areavalues surrounding the outward and return curves werepresented as thixotropy. Stress-dependent measurements
were conducted at 25°C and 37°C at a constantfrequency (1 Hz) to determine the storage modulus (G'),
indicating solid-like properties, and the loss modulus(G"), indicating liquid-like properties.
3. Results and Discussion

2.1. Materials
Posterisan® forte ointment (lot: 7A187, Maruho Co.,
Ltd., Osaka, Japan) was utilized as the brand-namedrug, while Hemoporison® ointment (lot: G142, J-Dorph
Pharmaceutical Co., Ltd., Shiga, Japan) served as thegeneric drug. In terms of composition, both ointments
contained identical ingredients: dead Escherichia coli
flotation fluid and hydrocortisone, with purified lanolin,
white petroleum jelly, and phenol as additives (Table 1).
2.2. Ductility test of ointments
The viscosity and ductility of the injectable ointments
was evaluated using a parallel spread meter (Rigo,Tokyo, Japan). The diameter spread of the ointment
sandwiched between two glass plates was recorded for
up to 300 s. The relationship of the sample diameter tothe logarithmic value of the elapsed time was plotted.
Viscosity was compared based on the intercept valueof this straight line, while the ease of ductility of each
formulation was compared based on the slope of thestraight line. Ointment ductility tests were conducted
three times at 25°C and 37°C for each formulation.
2.3. Evaluation of viscoelasticity of ointments using arheometer
Rheological measurements of the ointments wereperformed using a HAAKE MARS rheometer (ThermoDuctility refers to the ability of a material to deform
under stress, which in the context of ointments relates
to their spread ability and ease of application. We
conducted experiments using a spread meter under varied
temperature conditions to assess both the reference andgeneric products. The ductility of Posterisan® forte andHemoporison® ointments were compared at two different
temperatures: room temperature (25°C) and bodytemperature (37°C) (Figure 1). At 25°C, both ointments
differed in their ductility levels. At 37°C, ductility
generally increased for both ointments, suggesting easierapplication on the skin. Posterisan ® Forte ointment
demonstrated a more facile spread compared to theHemoporison® ointment, with a significant difference
observed under both temperature conditions. To
quantitatively com-pare the flow and spread, we utilized
the following equation:
S = (D2 -D1) / log10 (T2 / T1) + IC [eq. 1]
where S and IC indicate slope and intercept of theequation 1, respectively; D1 and D2 indicate diameter ofspread (mm) after time duration T1 and T2 (s).
T1, T2: Measurement time (s) T2 > T1, 5 ≤ T1 andT2 ≤ 100,
ΔT = (T2 −T1 ) > 40 [eq. 2]
The slope of the graph in Figure 1 indicates greater

Table 1. Composition of the ointments used in the study
NameCompany

Active pharmaceutical ingredients

Additive 1

Additive 2

Additive 3

Brand-name

Posterisan® forte
ointment

Maruho Co., Ltd.,
Osaka, Japan

0.163 ml of a suspension solutionof dead E. coli bacteria (containingapproximately 259 million bacteria)
and 2.5 mg of hydrocortisone per Japan
Pharmacopoeia

RefinedlanolinWhite
Vaseline

PhenolGeneric-drug

Hemoporison ®
ointment

J-Dorph PharmaceuticalCo., Ltd., Shiga, Japan

0.163 ml of a suspension solutionof dead E. coli bacteria (containingapproximately 259 million bacteria)
and 2.5 mg of hydrocortisone per Japan
Pharmacopoeia

RefinedlanolinWhite
Vaseline

Phenolwww.ddtjournal.com

267

Drug Discoveries & Therapeutics. 2024; 18(4):265-268.

sample flow with a larger value. The sample flow (S)of Posterisan® Forte ointment differed between the twotemperatures, with S = 0.1184 at 25°C and S = 0.0908
at 37°C. Conversely, for the Hemoporison® ointment,
the sample flow values were almost identical, with S =0.0863 at 25°C and S = 0.0841 at 37°C. The spread wasdetermined from the intersetion of the vertical axes as
depicted in Figure 1 (T = 1). A higher IC value indicateslower viscosity and greater flow of the sample. For thePosterisan® Forte ointment, the IC values were almost
equal, with IC = 2.6784 at 25°C and IC = 2.7434 at37°C. Conversely, differences were observed for theHemoporison® ointment, with IC = 2.5005 at 25°C andIC = 2.6567 at 37°C (Table 2). These results indicate thatfor the Posterisan® Forte ointment, sample flow decreases
as the temperature increases, indicated by the decreasein S from 25°C to 37°C. However, for Hemoporison®
ointment, the difference in sample flow between the twotemperatures was very small, indicating minimal change
in sample flow with temperature increase. Overall,this suggests that the sample flow of Posterisan® Forteointment is more temperature-sensitive compared toHemoporison® ointment.
The characterization of thixotropic behavior entails
examining the area enclosed by the shear rate versus

shear stress curves for both the forward and reverse
directions, which delineates the yield history following theapplication of shear. The shear rate-dependent propertiesof Posterisan® Forte and Hemoporison® ointments at 25°C
are illustrated in Figure 2. Upon increasing the shear rate(dg/dt) from 0 to 500 s-1, the corresponding shear stressvalues (τ) approximately doubled, measuring 1,200 Pa
and 2,100 Pa for the Posterisan® Forte and Hemoporison®
ointments, respectively. Notably, the area beneath thereturn curve, indicative of thixotropy, exhibited notablediscrepancies between the two formulations. Specifically,the area for Hemoporison® ointment surpassed that ofPosterisan® Forte ointment.
Figure 3 shows the relationship between shear stresson the horizontal axis and the storage modulus (G') andloss modulus (G") on the vertical axis, both expressedon a logarithmic scale. For both ointments, the storagemodulus (G') at 25°C exhibited a linear region unaffectedby increasing shear stress and thus maintaining a solid-likestructure. The G' value within this linear region reflects theFigure 2. The rate-dependent thixotropic properties of Posterisan®
forte (red circles) and Hemoporison® (blue circles) ointments at25°C.

Figure 1. Ductility of Posterisan® forte (red circles) and Hemoporison®
(blue circles) ointments at 25°C (a) and 37°C (b).

Table 2. The slope and intercept values of Posterisan®
forte and Hemoporison® ointments at 25°C and 37°COintment
Posterisan® ForteHemoporison®

Temperature (°C)

slope value

Intercept value

253725370.1184
0.09080.08630.08412.67842.74342.50052.6567

Figure 3. The rate-dependent properties of Posterisan® forte andHemoporison® ointments at 25°C (a) and 37°C (b).

www.ddtjournal.com

Drug Discoveries & Therapeutics. 2024; 18(4):265-268.
hardness of the ointment, with Hemoporison® ointment(27,000 Pa) demonstrating higher hardness compared toPosterisan® Forte ointment (8,500 Pa). With increasing
shear stress, G' gradually decreased, followed by a rapid
decline with additional stress application. The comparison
by temperature revealed a notable disparity between theformulations at 25°C; however, at 37°C, both ointments
exhibited lower values than those at 25°C, suggestinga temperature-dependent alteration in their rheologicalproperties. At 37°C, the viscosity of Posterisan® Forteointment measured 800 Pa, whereas that of Hemoporison®
ointment was 2,200 Pa. Despite a decrease in viscosity
relative to 25°C, Hemoporison® maintained a higherviscosity, hinting at inherent differences in compositionor formulation. Regarding the loss modulus (G'),
Posterisan® Forte ointment exhibited a higher value at25°C, indicative of greater energy dissipation during
deformation, potentially influencing its flow anddeformation characteristics. The behavior at 37°C
indicated a convergence between the two formulations,with the loss modulus (G") closely mirroring the storage
modulus (G'). This convergence suggests a mitigated distinction between the formulations at elevated temperaturescompared to those at 25°C. These findings underscore thesignificance of temperature in modulating the rheologicalproperties of the formulations, revealing differential
responses under varying conditions.
The study provides valuable insights into therheological behavior of Posterisan ® Forte andHemoporison® ointments, highlighting differences in
spread ability, thixotropic properties, and stiffness between
the two formulations. Injectable ointments are preferred
to be easily extrudable from the tube at the intended
usage temperature of 25°C, indicating good spread ability.
Additionally, it is desirable for the ointment to maintain its
shape after injection at body temperature (37°C). Using a
spread meter, we compared the elongation of the ointments
at 25°C and 37°C, assuming the temperature during use
and after injection, respectively (Figure 1). At 25°C, theelongation of Posterisan® Forte ointment was significantly
higher than that of the Hemoporison ® ointment. Incontrast, at 37°C, Posterisan® Forte ointment tended
to elongate more, but not significantly more than theHemoporison® ointment. Posterisan® Forte demonstrated
superior spread ability, maintaining consistent flow values
across different temperatures, whereas Hemoporison®
exhibited greater thixotropic behavior and stiffness,
indicating potential advantages in applications requiring
reversible viscosity changes and increased rigidity. Thesevariations in rheological properties between brand-nameand generic ointments could impact patient experienceand treatment efficacy. Changes in fluidity and viscosity
may influence patient perception and application behavior,potentially affecting treatment outcomes and the risk ofside effects. Therefore, precise guidance on application
amounts is essential to ensure appropriate use andminimize potential adverse effects. Although generic drugs

268

are increasingly popular, concerns about their quality
persist among patients, particularly regarding differencesin additives and formulation properties (6). Althoughboth Posterisan® Forte and Hemoporison® ointments usedin this study share the same additives, discrepancies inphysical properties were observed. This emphasizes theimportance of understanding formulation characteristics,
including container hardness and injection diameter, which
may affect ointment behavior. Further research is needed
to explore the implications of these findings in clinicalpractice, considering individual differences in usability andtherapeutic efficacy. Additionally, ongoing investigation
into other drugs and their rheological properties iswarranted to optimize their use and enhance patient
outcomes in pharmaceutical and cosmetic applications.
Funding: None.
Conflict of Interest: The authors have no conflicts ofinterest to disclose.
References
1.

2.

3.

4.
5.
6.

Sakamaki H. Issues on medical expenditure and the roleof generic drugs – Considerations from an international
comparison of healthcare costs, pharmaceutical costa andmeasures for generic drug use promotion. Jpn J GenericMed. 2013; 7:5-16. (in Japanese)
Ogita Y, Takahashi Y, Honda T, Kikkawa Y, Machida Y,Sudo H. Comparison of quality characteristics of whitepetrolatums. Jpn J Pharm Health Care Sci. 2007; 33:613618. (in Japanese)
Atkinson MJ, Sinha A, Hass SL, Colman SS, Kumar RN,Brod M, Rowland CR. Validation of a general measureof treatment satisfaction, the Treatment Satisfaction
Questionnaire for Medication (TSQM), using a national
panel study of chronic disease. Health Qual Life Outcomes.
2004; 2:12.
Zaghloul SS, Goodfield MJD. Objective assessment ofcompliance with psoriasis treatment. Arch Dermatol. 2004;
140:408-414.
Nakamura S, Ogawa K, Sameshima T, Masayoshi Y. A
study of the usability of a pouring container by elderlypersons. Jpn J Ergon. 2007; 43:154-155. (in Japanese)
Yamamoto T, Ito N, Shimada A, Takahashi Y, Tominaga Y,Nakano D, Hisai N, Fujii H, Onodera S, Harada Y. Patients'
tendency and change in consciousness toward genericdrugs. J Community Pharm Pharm Sci. 2017; 9:169-174. (inJapanese)

Received July 8, 2024; Revised August 9, 2024; Accepted
August 20, 2024.
*Address correspondence to:Motoki Inoue, Department of Physical Chemistry, Hoshi
University, 2-4-41, Ebara, Shinagawa-Ku, Tokyo 142-8501,
Japan.
E-mail: inoue.motoki@hoshi.ac.jp
Released online in J-STAGE as advance publication August 29,2024.

www.ddtjournal.com