Impact of active pharmaceutical ingredient variables and oleaginous base on the in vitro drug release from ophthalmic ointments: An investigation using dexamethasone as a model drug.

The present study systematically investigates the impact of active pharmaceutical ingredient (API) variables and oleaginous base characteristics on the in vitro release (IVR) performance of ophthalmic ointments, utilizing dexamethasone as a model drug. The interplay between selected attributes (i.e., particle size distribution, crystallinity, and polymorphic form for API, and rheological factors for compendial-grade white petrolatum) and IVR performance was investigated. APIs from different vendors exhibited variations in crystallinity and polymorphism. Ointments containing amorphous dexamethasone presented higher release amounts/rates compared to crystalline counterparts, emphasizing the role of physical state in release kinetics. Variations in particle size of this lipophilic API (5.4 - 21.2 µm) did not appear to impact IVR performance significantly. In contrast, white petrolatum's rheological attributes, which varied substantially within USP-grade petrolatum, were found to critically affect the drug release rate and extent of the ointment. The study's comprehensive analysis establishes a coherent connection between the quality attributes of both API and petrolatum and IVR, delineating their intricate interdependent effects on ophthalmic ointment performance. These findings provide reference to formulation design, quality control, and regulatory considerations within the pharmaceutical industry, fostering a robust foundational understanding of commonly overlooked quality attributes in ophthalmic ointments.

Development and Evaluation of Biocompatible Topical Petrolatum-liquid Crystal Formulations with Enhanced Skin Permeation Properties.

Transdermal administration represents a major advancement over traditional pharmaceutical dosing methods. However, a frequent issue is inadequate penetration of the active medicinal component through the skin. As a result, in the current research, we assessed the utility of newly developed petrolatum-liquid crystal (LC) ointment formulations and characterized their biocompatibility and function in the transdermal drug delivery system. To begin, we made petrolatum-LC formulations using p-aminobenzoic acid (PABA) as a hydrophilic model molecule. The viscosity, small-angle X-ray scattering (SAXS), particle diameters, and z-potential were measured to assess the physicochemical properties of the formulations. A dialysis release technique was used to evaluate medication release from petrolatum-LC formulations. In vitro testing was performed to determine the potential to enhance skin penetration. The biocompatibility of the produced formulations was further tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and single-cell gel electrophoresis. According to the results, the novel petrolatum-LC formulations are biocompatible and effective in forming hexosomes. PABA skin penetration was significantly enhanced by the new petrolatum-LC formulations. According to this study, petroleum-LC formulations are more efficient than commercial petrolatum in terms of skin permeability improvement and PABA skin concentration.

A Method for Measuring the Surface Free Energy of Topical Semi-solid Dosage Forms.

Our aim was to determine the surface free energy (SFE) of semi-solid dosage forms (SSDFs) by establishing a reproducible method for measuring the contact angle of liquids to SSDFs. Four SSDFs were used: petrolatum, an oil/water (O/W) and a water/oil (W/O) cream, and an alcohol-based gel. The SSDFs were evenly spread on a glass slide, and the change in contact angle over time was measured by dropping water, glycerol, diiodomethane and n-hexadecane as the test liquids. Depending on the combination of test liquid and SSDF, the contact angle was either constant or decreased in an exponential manner. Contact angles may have decreased in an exponential manner because the reaction between the test liquid and the SSDF altered the interfacial tension between the two phases and changed the surface tension of the test liquid and the SFE of the SSDF. The contact angle of the test liquid to the SSDF could be determined reproducibly using the initial contact angle immediately after dropping the liquid on the SSDF as the contact angle before reaction. Using the obtained contact angles and the Owens-Wendt-Rabel-Kaelble equation, we calculated the SFE and its component for the SSDFs tested and found that the results reflect the physicochemical properties of SSDFs. Furthermore, the work of adhesion (WA) of the SSDF to Yucatan micropig skin was calculated using the SFE for the SSDFs. Interestingly, the WA values for all SSDFs tested were comparable.

Effects of Manufacturing Conditions on Pharmaceutical Properties of Petrolatum Ointment-Distribution of Hydrocarbon.

Petrolatum ointment, which is an oleaginous ointment, is generally produced through manufacturing processes such as melting, mixing, and cooling. In this type of semisolid formulation, the manufacturing conditions of each process are empirically known to affect the quality of the resultant preparation; however, in many cases, the details of the factors are unclear. To clearly investigate the influence of the pharmaceutical properties of petrolatum ointments, we manufactured several ointments while changing the conditions of the mixing and cooling process after melting white petrolatum. As a result, the temperature at the termination was determined to influence the pharmaceutical properties of the final product. To investigate these phenomena, each petrolatum ointment sample was examined via digital microscopy and laser Raman analysis, and the distribution of the liquid-solid parts of samples was investigated. The internal structure of the ointment sample manufactured at a mixing-stop temperature of 40 °C, the needle crystals and the spherical aggregates surrounding them appropriately coexisted, while the structure exhibited a state wherein the two were linked in a semisolid phase. Meanwhile, for the ointment sample manufactured under the lowest mixing-stop temperature of 25 °C, the liquid part and the spherical aggregates were clearly separated, indicating that the liquid part was easily separated from ointments. In addition, the distribution of the hydrocarbons among the samples was measured via GC-MS; no significant difference in chemical structure was observed. In conclusion, the internal structure of the petrolatum ointment was changed by the manufacturing conditions, and this affected the pharmaceutical properties.

Replacing Synthetic Ingredients by Sustainable Natural Alternatives: A Case Study Using Topical O/W Emulsions.

With the increasing debate on sustainability, there is a strong market trend to formulate more sustainable products for topical application. Several studies emphasize the potential applications of natural, organic, or green chemistry-derived ingredients, but comparative studies between conventional ingredients and sustainable alternatives are lacking. This type of study is considered an excellent baseline and time-saving strategy for future studies. In addition, one of the main challenges of replacing ingredients by sustainable alternatives in topical vehicles is to maintain high-quality products. Thus, the main goal of this research study was to create a well-defined strategy supported by specific experimental data for the development of sustainable topical vehicles with high-quality standards. The study was designed to evaluate the effects of replacing conventional ingredients (e.g., hydrocarbons, silicones, and preservatives) by sustainable ones on the physical, chemical, and microbiological features of topical emulsions. Additionally, in vivo assessment studies were performed to evaluate the safety, biological efficacy, and sensorial aspects of the developed formulations. The results obtained showed that the replacement of ingredients by sustainable alternatives has an effective impact on the physicochemical and structural properties of the emulsions, mainly on their rheological behavior. However, using appropriate strategies for ingredient selection and rheological adjustment, it is possible to overcome some barriers created by the use of natural raw materials, thus developing appealing and high-quality sustainable topical vehicles.

Physicochemical attributes of white petrolatum from various sources used for ophthalmic ointment formulations.

Excipients from different sources may lead to significant differences in the performance of drug products, posing challenges in product quality control. A previous report showed that the drug release rates from ophthalmic ointments were affected by source variation of white petrolatum. To understand the physicochemical properties including the microstructure of white petrolatum and the impact of this on the performance of finished products, the following were investigated: rheological properties, thermal analysis (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)), as well as structural characteristics (polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS)). The rheological parameters may be indicative of the drug release rate of the finished ophthalmic ointments when using a process involving hot-melting with immediate cooling. The white petrolatum from the four different sources also showed different thermal behavior. According to SAXS and WAXS, all of the petrolatum showed semi-crystalline behavior with different extents of crystallinity (from 9.5% to 16.9%). The crystalline domains of the petrolatum are ordered in an orthorhombic structure forming lamellar sheets with a periodicity from 9.1 nm to 9.9 nm. An in-depth understanding of the semi-crystalline structure was obtained and it provided valuable information for formulation optimization and characterization of petrolatum-based products.

The benefits of photoacoustics for the monitoring of drug stability and penetration through tissue-mimicking membranes.

The paper demonstrates the potential of photoacoustics for the identification of the mechanisms underlying drug transport through tissue-mimicking systems. Photoacoustic experiments were performed for a model transdermal delivery system, consisting of drug dithranol (in pharmaceutical form) and dodecanol-collodion (DDC) membrane. The spectroscopic data revealed a single-path photodegradation of dithranol in Vaseline (dithranol â†’ danthrone, characterized by the 1st order decay rate of (7.85 ± 0.31)·10-4 s-1), and a multipath degradation in the DDC system, involving danthrone and the unknown compound (characterized by the absorption band at ~400 nm) as the final products. The desorption experiments performed enabled the identification of the unknown compound as the photodegradation product of dithranol molecules bound to the membrane matrix. The result led to the incorporation of the adsorption effects and heterogeneous structure of the membrane into the hydrodynamical model of mass transport. The model was tested against the photoacoustic depth-profiling data for dithranol permeation through DDC. The analysis allowed the dispersion and advection coefficients to be determined (D' = (2.05 ± 0.03)⋅10-9 cm2 s-1 and va' = (-5.55 ± 0.05)⋅10-7 cm s-1, respectively). Moreover, it was found, that the dithranol photodegradation rate in the non-steady state system is slower compared to the steady-state case; the effect was attributed to different permeation rates of dithranol and mobile Vaseline particles through the membrane.

Clinical wear of approximal glass ionomer restorations protected with a nanofilled self-adhesive light-cured protective coating.

OBJECTIVE: High viscous glass ionomer cement (GIC) has gained popularity as a restorative material; however, high wear is pointed as one of the major drawbacks of this material. Protective surface coatings were developed to protect GIC from water contamination with the additional advantage of occluding any surface cracks or porosities commonly found in this material, possibly resulting in an increased wear resistance of the restorations. The objective of this study was to investigate the clinical wear of GIC approximal restorations in primary molars protected either with a nanofilled self-adhesive light-cured protective coating (NPC) or with petroleum jelly. MATERIAL AND METHODS: Approximal caries lesions in primary molars from 32 schoolchildren previously enrolled in another clinical trial were included in this investigation. GIC restorations were performed according to the Atraumatic Restorative Treatment approach and protected with either petroleum jelly or a NPC. Impressions of the restored hemiarch were done after 1 day and 6, 12, 24 and 36 months. The impressions were scanned in a 3-D appliance and the obtained images were superimposed using an appropriate computer software. Two-way ANOVA for repeated measures and Tukey's post-hoc test were used to analyze the wear of restorations (α=5%). RESULTS: A significant difference was found between the two groups, with a wear protection offered by the application of a NPC. Conclusion: These results suggest that the application of a NPC has a protective effect on the clinical wear of approximal GIC restorations in primary teeth.

Perspectives on Physicochemical and In Vitro Profiling of Ophthalmic Ointments.

Ophthalmic ointments are unique in that they combine features of topical drug delivery, the ophthalmic route and ointment (semisolid) formulations. Accordingly, these complex formulations are challenging to develop and evaluate and therefore it is critically important to understand their physicochemical properties as well as their in vitro drug release characteristics. Previous reports on the characterization of ophthalmic ointments are very limited. Although there are FDA guidance documents and USP monographs covering some aspects of semisolid formulations, there are no FDA guidance documents nor any USP monographs for ophthalmic ointments. This review summarizes the physicochemical and in vitro profiling methods that have been previously reported for ophthalmic ointments. Specifically, insight is provided into physicochemical characterization (rheological parameters, drug content and content uniformity, and particle size of the API in the finished ointments) as well as important considerations (membranes, release media, method comparison, release kinetics and discriminatory ability) in in vitro release testing (IVRT) method development for ophthalmic ointments. Graphical Abstract Summary of the physicochemcial profiling and in vitro drug release testing (IVRT) for ophthalmic ointments.

Influence of Manufacturing Process Variables on the Properties of Ophthalmic Ointments of Tobramycin.

PURPOSE: The main purpose of this study was to evaluate qualitative (Q1) and quantitative (Q2) equivalent oleaginous ophthalmic ointments of tobramycin (TOB) with different physicochemical properties and identify critical process/quality attributes using various in vitro methods of characterization. METHODS: Various sources of petrolatum and TOB, and two mixing methods were employed to generate Q1/Q2 equivalent ointments. Characterization studies included content uniformity, microscopy, modulated temperature differential scanning calorimetry (MTDSC), gas chromatography-mass spectrometry (GC/MS), thermogravimetric analysis (TGA) and rheology. RESULTS: The particle size distribution of TOB influenced the content uniformity of ointments. Differences in the MTDSC endothermic and exothermic peaks of TOB suggested the presence of different polymorphic forms. GC/MS revealed variations in the composition and distribution of linear and branched hydrocarbons of petrolatums. Differences were also observed in the TGA derivative weight loss peaks demonstrating differences in the composition of petrolatum that may be the source of the observed variations in the rheological parameters of the ointments. CONCLUSIONS: Source and composition of the petrolatum played a more critical role in determining the rheological properties compared to the method of preparation. Results demonstrated the impact of the source of TOB, excipients and manufacturing processes on the quality attributes of TOB ophthalmic ointments.

Fabrication of optimized skin biomimics for improved interfacial retention of cosmetic emulsions.

Retention of hydrophobic active agents on human skin following the use of skin-care formulations is an important indication of the performance of the deposited product. We have developed a novel system which replicates the interaction between human skin and a cosmetic emulsion to systematically establish and characterize the key parameters driving the retention process at the interface. This included a comprehensive study of the skin's biology and physical properties which influenced the process, the fabrication of advanced, improved skin biomimics, the formulation of a cosmetic model-system emulsion, comprising a hydrophobic active agent i.e. petrolatum, commonly used in cosmetic products, the development of a dedicated and highly consistent deposition rig with a corresponding cleaning set-up and the systematic characterization of retention processes on the developed mimics. This study further explores the interplay of petrolatum with skin biomimics and studies the mechanisms that give rise to improved interfacial retention. Petrolatum has been found to create an occlusive layer on the skin mimic, displaying high coverage from emulsion formulations. The large particle size emulsions yielded improved retention on the developed skin biomimics due to the microstructure of the emulsion and the counter effect of the surfactant.

Wet-wrap therapy with halometasone cream for severe adult atopic dermatitis.

BACKGROUND: Currently there is no cure for severe atopic dermatitis (AD). Wet-wrap therapy (WWT) has also been used to treat pediatric AD and shown a satisfactory effectiveness, but clinical evidence supporting the use of WWT on severe adult AD is still insufficient. METHODS: Twelve patients (eight men and four women) with severe AD (SCORing Atopic Dermatitis [SCORAD] score ≥ 50) treated between January 2015 and September 2017 in our hospital were included. The patients underwent WWT (daily dose: 15 g halometasone cream+100g Vaseline ointment) twice daily for 2 h/session for 7 days. SCORAD, visual analog scale (VAS) for pruritus, investigator's global assessment (IGA), dermatology life quality index (DLQI) scores and serum cortisol levels were determined before and after the WWT. RESULTS: The patients (mean age: 58.9 ± 18.9 years; range: 27-85 years) had a median disease duration of 27.5 months. After the WWT, the average scores of SCORAD (28.79 ± 5.16 vs. 68.59 ± 8.61, 95%CI: 35.18-44.42), VAS (2.75 ± 0.62 vs. 7.5 ± 1.17, 95%CI: 4.14-5.36), IGA (1.83 ± 0.39 vs. 4.08 ± 0.51, 95%CI: 1.96-2.54), and DQLI score (8.33 ± 1.83 vs. 13.83 ± 2.79, 95%CI: 4.16-6.84) reduced significantly compared with the scores before the WWT (All P < 0.001). However, serum cortisol levels were not affected significantly by the WWT. Four patients complained of tolerable wet dressing-associated discomforts, which was resolved after the wet dressing was removed when the WWT was completed. For the 85-year-old man, serum cortisol levels were lower than the normal value after the WWT (3.67 µg/dL) but restored to the normal levels (13.44 µg/dL) 2 weeks after the WWT was ended. No other adverse events occurred. CONCLUSION: WWT can relieve pruritus, reduce skin lesions, and improve quality of life in adult patients with severe AD. Thus, WWT may be effective and safe for severe adult AD. Trial registration No. is ChiCTR1800014909 ( http://www.chictr.org.cn/index.aspx ).

The Role of Excipients in the Stability of Triamcinolone Acetonide in Ointments.

Degradation of triamcinolone acetonide (TCA) in an ointment was investigated. TCA appeared to be concentrated in propylene glycol (PG) which in turn is dispersed in a lanolin-petrolatum mixture. Two predominant degradation products were identified: a 21-aldehyde and a 17-carboxylic acid. The 21-aldehyde is formed after TCA is oxidized by O2, a reaction that is catalyzed by trace metals. Logically, the content of trace metals has a profound effect on the degradation rate. It was shown that trace metals are extracted from lanolin and petrolatum by PG, increasing the concentration in PG. In accordance with these findings, TCA degrades faster in PG that is present in the ointment formulation than in regular PG. The 21-aldehyde was confirmed to be a primary degradation product, while the 17-carboxylic acid was identified as a secondary degradation product. Based on the mechanism of degradation, the ointment can be stabilized by the addition of sodium metabisulfite which was shown to reside also in the PG phase within the ointment.

Study of petrolatum structure: Explaining its variable rheological behavior.

The rheological properties of petrolatum are dependent on both temperature and thermal history. How this thermal dependency can be explained is unclear. In the past it has been suggested that the structure of petrolatum consists of a three-dimensional crystalline network. This has been established using old microscopic techniques only. Therefore a study on the microstructure of petrolatum was conducted using rheometry, DSC, pulsed NMR, polarized light microscopy and synchrotron X-ray. The combination of these techniques show that petrolatum is composed of 21% solid material at room temperature. This consists of partly crystalline lamellar sheets which are packed in stacks. The occurrence of these lamellar sheets is temperature dependent and the number of lamellar stacks is dependent on thermal history. It was shown that rheological differences in petrolatum can be explained by the number of lamellar stacks present, where more lamellar stacks result in more rigid petrolatum.

Clinical wear of approximal glass ionomer restorations protected with a nanofilled self-adhesive light-cured protective coating

Abstract High viscous glass ionomer cement (GIC) has gained popularity as a restorative material; however, high wear is pointed as one of the major drawbacks of this material. Protective surface coatings were developed to protect GIC from water contamination with the additional advantage of occluding any surface cracks or porosities commonly found in this material, possibly resulting in an increased wear resistance of the restorations. Objective: The objective of this study was to investigate the clinical wear of GIC approximal restorations in primary molars protected either with a nanofilled self-adhesive light-cured protective coating (NPC) or with petroleum jelly. Material and Methods: Approximal caries lesions in primary molars from 32 schoolchildren previously enrolled in another clinical trial were included in this investigation. GIC restorations were performed according to the Atraumatic Restorative Treatment approach and protected with either petroleum jelly or a NPC. Impressions of the restored hemiarch were done after 1 day and 6, 12, 24 and 36 months. The impressions were scanned in a 3-D appliance and the obtained images were superimposed using an appropriate computer software. Two-way ANOVA for repeated measures and Tukey's post-hoc test were used to analyze the wear of restorations (α=5%). Results: A significant difference was found between the two groups, with a wear protection offered by the application of a NPC. Conclusion: These results suggest that the application of a NPC has a protective effect on the clinical wear of approximal GIC restorations in primary teeth.

Egg Albumen as a Fast and Strong Medical Adhesive Glue.

Sutures penetrate tissues to close wounds. This process leads to inflammatory responses, prolongs healing time, and increases operation complexity. It becomes even worse when sutures are applied to stress-sensitive and fragile tissues. By bonding tissues via forming covalent bonds, some medical adhesives are not convenient to be used by surgeons and have side effects to the tissues. Here egg albumen adhesive (EAA) is reported with ultrahigh adhesive strength to bond various types of materials and can be easily used without any chemical and physical modifications. Compared with several commercial medical glues, EAA exhibits stronger adhesive property on porcine skin, glass, polydimethylsiloxane. The EAA also shows exceptional underwater adhesive strength. Finally, wound closure using EAA on poly(caprolactone) nanofibrous sheet and general sutures is investigated and compared in a rat wound model. EAA also does not show strong long-term inflammatory response, suggesting that EAA has potential as a medical glue, considering its abundant source, simple fabrication process, inherent nontoxicity, and low cost.

Evaluation of Moisturizing Effect of Heparinoid Ointment (Hirudoid Soft Ointment) Diluted by White Petrolatum (Propeto).

Steroid ointments are frequently mixed with moisturizer. It was reported that steroid ointments mixed with moisturizer increase permeability. There are only few studies done on the permeability of the moisturizer. We researched moisturizing effect of heparinoid ointment (Hirudoid Soft ointment) diluted with white petrolatum (Propeto) on the dry skin models by measuring water content of stratum. Two to four fold dilution of Hirudoid to white petrolatum resulted in a significant decrease in the moisturizing effect of the active ingredient. There was no significant difference in moisturizing effect between four times diluted mixture and white petrolatum alone. This leads to the conclusion that steroid ointment mixture with moisturizer is frequently used, but we should take more caution regarding the decrease of moisturizing effect.

Effects of different base agents on prediction of skin irritation by sodium lauryl sulfate using patch testing and repeated application test.

Animal testing for cosmetics was banned in the European Union (EU) in 2013; therefore, human tests to predict and ensure skin safety such as the patch test or usage test are now in demand in Japan as well as in the EU. In order to investigate the effects of different bases on the findings of tests to predict skin irritation, we performed patch testing (PT) and the repeated application test (RAT) using sodium lauryl sulfate (SLS), a well-known irritant, dissolved in 6 different base agents to examine the effects of these bases on skin irritation by SLS. The bases for PT were distilled water, 50% ethanol, 100% ethanol, a gel containing 50% ethanol, white petrolatum, and hydrophilic cream. The concentrations of SLS were 0.2% and 0.5%. Twelve different base combinations were applied to the normal back skin of 19 individuals for 24h. RAT was performed with distilled water, 50% ethanol, 100% ethanol, a gel containing 50% ethanol, white petrolatum, and hydrophilic cream containing SLS at concentrations of 0.2%, 2%, and 5%, being applied to the arms of the same PT subjects. The test preparation of each base was applied at the same site, with 0.2% SLS being used in the first week, 2% SLS in the following week, and 5% SLS in the final week. The results of PT revealed that skin irritation scores varied when SLS at the same concentration was dissolved in a different base. The results of RAT showed that although skin irritation appeared with every base at a concentration of 5%, the positive rate was approximately the same. In conclusion, our results suggest that skin irritation elicited in PT depends on the base, while in RAT, it does not depend on the type of base employed.

Elucidation of the variability in consistency of pharmacopoeia quality petrolatum.

The Pharmacopeia monograph for petrolatum poorly defines the material's physical properties. Indeed, differences between petrolatum grades can be substantial; yield stress varies between 65 and 280 Pa which can be compared with the consistency of respectively thin cream or thick ointment. This variation is not only due to differences in composition or refining process but also as a result of different processing; for example, thermal history influences petrolatum structure considerably. Slow cooling of petrolatum resulted in a yield stress of 26 Pa and fast cooling in 79 Pa. X-ray showed that crystallinity was 0.7% for the first cooling case and 1.5% for the second one. Crystallite size was estimated to be 20-50 nm. To investigate if this relatively small difference in crystallinity may induce the difference in consistency, 15 nm SiO2 particles were added to petrolatum. Indeed, a small increase in SiO2 concentration led to a major increase in yield stress. This was argued to be due to the small size of the particles, resulting in a large increase in absolute number of particles. The Pharmacopeia does not unambiguously define the pharmaceutical excipient petrolatum. As a consequence, the formulator has to take care of selecting the appropriate grade as well as to carefully control the processing of the material in order to achieve a consistent pharmaceutical product.

Effects of Manufacturing Conditions on Pharmaceutical Properties of Petrolatum Ointment.

Oleaginous white petrolatum ointment (WP ointment) is one of the most commonly used dosage forms in the preparation of topical products. In general, WP ointments containing medium chain fatty acid triglycerides (MCT) are manufactured through a process of melting, mixing, agitating, and cooling. To investigate the pharmaceutical properties of WP ointments in greater detail, we examined manufacturing factors which could potentially influence the pharmaceutical properties of the finished product. WP ointment samples containing 10% MCT were stirred with a homogenizer and a paddle mixer at 65°C, then the homogenizer was stopped. Next, the paddle-mixer was stopped at several planned temperature points at which different samples were taken. Each sample was then cooled under the following planned conditions: rapid-cooling [-50°C/h] and slow-cooling [-7.5°C/h]. The pharmaceutical properties of each WP ointment sample, along with the appearance (Optical/digital microscope), hardness (Rheometer), and bleeding ability (100 Mesh wire-net cone) were measured. Then, release profiles were performed with a WP ointment using the model active ingredient Vitamin D. As a result, high hardness, low bleeding ability and low release profile were observed in the WP ointment samples that were manufactured under the condition of stopping the paddle-mixer at 40°C. However, the influence of cooling speed was observed to affect only hardness. Through optical microscopic observation, it was found that the appearance of WP ointment samples differed depending on the conditions under which they were manufactured. In this study, it was clear that the pharmaceutical properties of WP ointment samples were particularly influenced by the paddle-mixer stopping temperature.