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It is essential as well as challenging to develop a reliable in vitro release testing method for determining whether differences in release profiles exist between qualitatively and quantitatively equivalent ophthalmic ointment formulations. There is a lack of regulatory guidance on in vitro release testing methods for ophthalmic formulations. Three different in vitro release testing methods: 1) USP apparatus 4 with semisolid adapters; 2) USP apparatus 2 with enhancer cells; and 3) Franz diffusion cells were investigated. Qualitatively and quantitatively equivalent ointments were prepared via hot melting and simple mixing methods using four different sources of excipients (i.e. white petrolatum). The ointment formulations were characterized for content uniformity, particle size, and rheological parameters. All the formulations showed adequate content uniformity and similar particle size. The ointments prepared via the hot melting processes showed higher rheological parameters, as did the ointments prepared using ‘white’ petrolatum that exhibited a yellowish color. The three in vitro release testing methods were compared and evaluated for reproducibility, discriminatory capability, and correlation with the rheological parameters. Compared with the compendial methods, the non-compendial method (Franz diffusion cells) showed poorer reproducibility. All three methods possessed the ability to discriminate between the ophthalmic ointments with manufacturing differences. However, the USP apparatus 4 method displayed the largest margin of discrimination between the release profiles of the different ophthalmic ointments. In addition, the in vitro release rate obtained using the USP apparatus 4 method showed the strongest logarithmic linear correlation with the rheological parameters (Power law consistency index (K value) and crossover modulus) compared to the other two methods.

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.

Mucoadhesive films represent the most developed medical form of buccal application. Despite the intense focus on buccal film-based systems, there are no standardized methods for their evaluation, which limits the possibility of comparison of obtained data and evaluation of the significance of influence of formulation and process variables on properties of resulting films. The used principal component analysis, together with a partial least squares regression provided a unique insight into the effects of in vitro parameters of mucoadhesive buccal films on their in vivo properties and into interdependencies among the studied variables. In the present study eight various mucoadhesive buccal films based on mucoadhesive polymers (carmellose, polyethylene oxide) were prepared using a solvent casting method or a method of impregnation, respectively. An ethylcellulose or hydrophobic blend of white beeswax and white petrolatum were used as a backing layer. The addition of polyethylene oxide prolonged the in vivo film residence time (from 53.24 ± 5.38–74.18 ± 5.13 min to 71.05 ± 3.15–98.12 ± 1.75 min), and even more when combined with an ethylcellulose backing layer (98.12 ± 1.75 min) and also improved the film’s appearance. Tested non-woven textile shortened the in vivo film residence time (from 74.18 ± 5.13–98.12 ± 1.75 min to 53.24 ± 5.38–81.00 ± 8.47 min) and generally worsened the film’s appearance. Mucoadhesive buccal films with a hydrophobic backing layer were associated with increased frequency of adverse effects.

The aim of this study was to design porous matrix beads for floating drug delivery using enteric polymer, Eudragit® L and various amounts of waxes (0, 0.1, 0.5, 1, 2 and 3% w/w). In this study, wax containing cetyl alcohol and white petrolatum was utilized to produce pores using a wax removal technique. To prepare the beads, Eudragit® L, metronidazole and wax were dissolved in acetone and then extruded into dichloromethane. The effect of the amount of wax on the floating and drug release behavior of the Eudragit® L beads was determined. After the extruded product was immersed in dichloromethane, wax dissolved out from the formed beads, resulting in a porous structure. The prepared beads could float in simulated gastric fluid for more than 10 hours. Different amounts of wax had an effect on the drug release. We found that when the percentage of wax increased, the drug release was higher while the beads remained floating. The results suggest that Eudragit® L beads could be used as a carrier for an intragastric floating drug delivery system.

Citronella oil (CO) has been reported to possess a mosquito-repellent action. However, its application in topical preparations is limited due to its rapid volatility. The objective of this study was therefore to reduce the rate of evaporation of the oil via microencapsulation. Microcapsules (MCs) were prepared using gelatin simple coacervation method and sodium sulfate (20%) as a coacervating agent. The MCs were hardened with a cross-linking agent, formaldehyde (37%). The effects of three variables, stirring rate, oil loading and the amount of cross-linking agent, on encapsulation efficiency (EE, %) were studied. Response surface methodology was employed to optimize the EE (%), and a polynomial regression model equation was generated. The effect of the amount of cross-linker was insignificant on EE (%). The response surface plot constructed for the polynomial equation provided an optimum area. The MCs under the optimized conditions provided EE of 60%. The optimized MCs were observed to have a sustained in vitro release profile (70% of the content was released at the 10th hour of the study) with minimum initial burst effect. Topical formulations of the microencapsulated oil and non-microencapsulated oil were prepared with different bases, white petrolatum, wool wax alcohol, hydrophilic ointment (USP) and PEG ointment (USP). In vitro membrane permeation of CO from the ointments was evaluated in Franz diffusion cells using cellulose acetate membrane at 32 °C, with the receptor compartment containing a water-ethanol solution (50:50). The receptor phase samples were analyzed with GC/MS, using citronellal as a reference standard. The results showed that microencapsulation decreased membrane permeation of the CO by at least 50%. The amount of CO permeated was dependent on the type of ointment base used; PEG base exhibited the highest degree of release. Therefore, microencapsulation reduces membrane permeation of CO while maintaining a constant supply of the oil.

Dermatologists can decrease unnecessary use of antimicrobial agents by avoiding them in situations wherein good evidence indicates that they are ineffective. Controlled trials indicate that antimicrobial agents are unhelpful in treating cutaneous abscesses, inflamed epidermal cysts, uninfected atopic eczema, and cutaneous ulcers caused by venous insufficiency or diabetes in the absence of significant contiguous soft-tissue inflammation. Prophylactic antibiotics are rarely appropriate for routine dermatologic surgery and are not indicated for patients who have prosthetic joints or vascular grafts. They are recommended only for a small group of patients who have abnormal cardiac valves, and then only with surgery involving clearly infected skin or soft-tissue. Topical antibiotics are no better than white petrolatum in covering sutured wounds, and with moist occlusive dressings, no ointment is necessary.

Summary To study the in vivo penetration and skin distribution of hypericin, the compound (0.1%) was formulated in 10 different vehicles that are commonly used in pharmaceutical compounding, and applied on the skin of hairless mice for 4 h. After application of hypericin in PEG ointment, white petrolatum or unguentum emulsificans, fluomicroscopic analysis of skin sections revealed penetration to be confined to the stratum corneum. On the contrary, Beeler base, unguentum sorbatis 100 and cremor non ionicus caused penetration of hypericin in the viable epidermis. To reduce the prominent depot formation in the stratum corneum, which was observed irrespectively of the formulation applied, hypericin was esterified into its hydrolyzable acetate derivative. The influence of esterification proved to be substantial when hypericin acetate (0.15%) was incorporated in unguentum sorbatis 100, as hypericin-related fluorescence could be detected deeply within the dermis. Moreover, accumulation in the sebaceous glands was found to be prominent. These results indicate the value of further studies regarding the application of hypericin and hypericin acetate as topical photosensitizers for photodynamic therapy.

Casarotto RA, Adamowski JC, Fallopa F, Bacanelli F. Coupling agents in therapeutic ultrasound: acoustic and thermal behavior. Arch Phys Med Rehabil 2004;85:162–5. Objective To compare transmissivity data and thermal behavior of 4 coupling media. Design Experimental. Setting Postgraduate rehabilitation program in Brazil. Specimens Four coupling media: gel, mineral oil, white petrolatum, and degassed water. Interventions Not applicable. Main outcome measures The transmission, attenuation, reflection coefficient, and acoustic impedance of gel, mineral oil, white petrolatum, and degassed water were measured with a density measurement cell. The temperature variation in the therapeutic ultrasound transducer was measured with a thermocouple. Results The transmissivity data showed that the water and gel presented the highest transmission coefficient, the lowest reflection, and an attenuation coefficient and acoustic impedance close to that of the skin. The thermal data revealed the highest heating in the transducer during the insonation with white petrolatum and mineral oil, resulting from the thermal conductivity features of each medium. Conclusions Transmissivity data obtained showed that water and gel present the best acoustic features. In ultrasound therapy, with the direct contact technique using thin layers of coupling agents, any product may be used, because the effect of the attenuation coefficient does not play a significant role when layers are as thin as those used in this experiment.

The effects of gamma irradiation on petrolatum eye ointment base (EOB) and its ingredients (white petrolatum, liquid paraffin, and wool fat) were studied at different irradiation doses. Forty-one volatile radiolysis products were detected and identified by a combined system of headspace-gas chromatography-mass spectrometry (HS-GC-MS). The characteristics of the radiolysis products and the degradation pathway were discussed in each case, respectively. GC method demonstrates that the component distribution patterns of eye ointment as well as its individual ingredients have no differences before and after gamma irradiation. The influence of gamma treatment on EOB was quantitatively determined at 15, 25 and 50 kGy. The concentrations of the radiolysis products increase linearly with increasing doses. Both qualitative and quantitative data show that irradiated eye ointment is safe for human use.

Background: Adapalene is a naphthoic acid derivative with retinoid activity that is effective in the treatment of mild to moderate acne vulgaris. Objective: This study assessed the cumulative irritation potential of adapalene gel (0.1%) and adapalene cream (0.1%) compared with that of erythromycin (4%)/tretinoin (0.025%) solution, erythromycin (4%)/tretinoin (0.025%) gel, erythromycin (2%)/isotretinoin (0.05%) gel, and white petrolatum (negative control). Methods: This was a single-center, randomized, controlled, investigator-blinded, intraindividual comparison study in healthy subjects with normal skin. The cumulative irritation assay (patch test) was used to assess the potential for irritation (including erythema) of the treatments. Each subject received all study treatments, randomly applied under occlusion (patch), to sites on either side of the midline on the mid-thoracic area of the back. All patches were applied to the same sites throughout the study, unless the degree of reaction to the treatment or adhesive necessitated removal. For 3 weeks, each test material was applied daily, Monday through Friday, for ∼24 hours; the Friday patches were left in place over the weekend for ∼72 hours. Results: All 36 subjects (26 men, 10 women; age, 18–49 years [mean, 30 years]) completed the study. In the course of the study, all subjects had ≥1 application discontinued prematurely on ≥1 site due to intolerance. There were no discontinuations with white petrolatum. All erythromycin/tretinoin gel patches were discontinued at day 10; 35 of 36 erythromycin/isotretinoin gel patches were discontinued at day 9; and 35 of 36 erythromycin/tretinoin solution patches were discontinued at day 11 or day 17. The adapalene products, although slightly more irritating (mean cumulative irritation index, 0.25–1) than white petrolatum, were significantly less irritating than the erythromycin/tretinoin and erythromycin/isotretinoin products ( P Conclusions: Adapalene gel and cream were well tolerated, with possible benefits for compliance. Their low irritation potential should be considered when prescribing a topical retinoid for the treatment of acne vulgaris.

The influence of different ratios of individual components (silicone surfactant, hydrophilic and lipophilic phase) on the viscoelastic behaviour of semisolid lipophilic emulsion systems was studied. The creams were prepared according to a preliminary experimental design (mixture design). The content of all three phases was varied: surfactant (1–5%), purified water (from 40 to 90%) and white petrolatum (5–59%). Oscillatory rheometry was used as the most appropriate experimental method for the evaluation of the emulsions. The rheological properties were influenced by the ratio of the components. For highly concentrated systems the predominant elastic response in the whole frequency range was measured. The cross-over point is characteristic for the concentrated systems. For the low concentrated systems, viscous behaviour is predominant. Rheometry has also been employed to follow and evaluate physical stability as one of the critical factors of emulsion systems. The dynamic rheological parameter, tan δ , has been chosen as the basis for developing mathematical models (linear, polynomial, neural) to forecast stability related to the content of the separate components in emulsion systems. After testing the linear models their non agreement to statistical criteria for a good model F reg , F lof , CC, DC, and RMS was found. The two-level neural network has been proven to be a statistically acceptable model, as were the polynomials of the second order. The two-level neural network model was also evaluated and the results have shown a great degree of reliability. The prediction of tan δ using a neural network model was found to be of great interest for the contemporary pharmaceutical formulation design because a lot of additional testing can be omitted.

Ketoprofen (KP) is a potent non-steroidal anti-inflammatory drug which is used for the treatment of rheumatoid arthritis. The oral administration of KP can cause gastric irritation and renal adverse effects. Topical application of the drug can bypass gastrointestinal disturbances and provide relatively consistent drug levels at the site of action. Since the efficacy of an ointment depends on the type of ointment base and the concentration of the drug, four different bases (white petrolatum, cold cream, hydrophilic ointment and Carbopol 940 gel) were used at 1, 3, 5, 7 and 10% concentrations of KP to evaluate the effect of ointment base and concentration. The general rank order of the drug release was found to be: Carbopol gel > hydrophilic ointment > cold cream > white petrolatum. There was a positive correlation between the concentration of KP and release rate for all bases except Carbopol gel. The in vivo percutaneous absorption of KP from different ointment bases at 3% concentration was studied by carrageenan-induced paw edema in mice. The rank order of the percent edema inhibition was as follows: Carbopol gel ≥ hydrophilic ointment > cold cream > white petrolatum. There was a good correlation between the in vitro and in vivo results.

In the course of investigating the effects of silicone surfactant (Abil WE 09®) on the microstructure of semisolid w/o emulsion systems with different water/oil ratios, only dispersed droplets of the internal water phase (1–15 μm size) were discovered in the gel network of white petrolatum. With increasing water content (from 40 to 90% w/w) the degree of dispersity was found to increase (microscopic analysis-polarized light microscopy and TEM). Experiments were also carried out using differential scanning calorimetry (DSC) and rheometry (rotational and oscillatory viscosimetry). The DSC results showed different behaviour of the investigated systems on controlled cooling. In semisolid emulsion systems with droplets small enough and of equal size, a homogeneous nucleation temperature was achieved. In emulsion systems containing a high percentage of water, the assumption that the behaviour of water was like that of the pure (bulk) water was acceptable. All semisolid emulsion systems exhibited pseudoplastic behaviour. Their viscoelastic properties determined using oscillation rheometry correlated well with rotational results.

We attempted to determine the level of sweat kallikrein (kininogenase) and to purify and characterize it using sweat collected over a white petrolatum barrier. Thermally induced eccrine sweat obtained from 24 healthy subjects showed kallikrein activity of 24.4 ng kinins generated/1 mg of sweat protein when heated plasma was used as the substrate and 16.1 ng kinin when purified low molecular weight bovine kininogen was used as the substrate. Sweat was sequentially purified by Sephacryl S-200, diethyaminoethyl Sephacel, and fast flow liquid chromatography Mono Q chromatography. Sweat kallikrein had a M(r) of 40,000 and was inhibited by aprotinin but not by soybean trypsin inhibitor. The peptide generated by sweat kallikrein was identified as lys-bradykinin using reverse phase high-performance liquid chromatography and by its amino acid sequence. Anti-human urinary kallikrein immunoglobulin G neutralized the sweat kallikrein activity completely, indicating that the sweat kallikrein is the glandular type. Purified sweat and salivary kallikrein showed similar M(r) and responses to inhibitors and antibodies. Using immunohistochemistry, kallikrein activity was localized in luminal ductal cells and in the peripheral rim of secretory coil segments, presumably the outer membrane of the myoepithelium. We also observed kininase activity in sweat at M(r) 160,000, which was inhibited by ethylenediamine tetraacetic acid, captopril, and angiotensin converting enzyme inhibitor peptide, indicating that it is kininase II (or angiotensin converting enzyme). Sweat also contains abundant non-kallikrein hydrolases for S-2266 and S-2302. The demonstration of glandular kallikrein, its tissue localization, and the presence of kininase II in sweat provide the basis for future studies on the physiologic role of the kallikrein/kinin system in the eccrine sweat gland.

The hydrolysis of the chemisorbate of p -hydroxybenzoic acid methyl ester (PHBAME) on porous silica (KG 100) incorporated in lipophilic vehicles such as liquid paraffin, synthetic oil Miglyol® 818 and white petrolatum was examined in dissolution media at pH 2 and 7.4, respectively. Chemisorbed PHBAME on KG 100 is released more rapidly in alkaline than in acidic dissolution fluids. Dispersions of the PHBAME-KG 100 chemisorbate in lipophilic vehicles modify the hydrolysis significantly. Drug release from chemisorbate dispersed in lipophilic vehicles may be controlled by the polarity of the vehicles. However, the viscosity of the vehicle, and not the polarity, exerts the strongest influence on the drug release.

An animal study was conducted to elucidate the role of ovalbumin (OA) in the development of eczematous lesions in intrauterine sensitized newborns. Four groups of pregnant guinea pigs were used: group A, immunized by oral administration of 1% OA in drinking water until parturition; group B, immunized by intradermal injection of OA with Freund's complete adjuvant; group C, immunized by both methods; and group D (control), not immunized. The newborn guinea pigs of each group were patch tested with 10% OA in white petrolatum. Positive reactions were seen in the newborns of groups B and C, but not in those in groups A and D. By enzyme-linked immunosorbent assay and passive cutaneous anaphylaxis, a high titre of OA-specific IgG was detected in the group B and C newborns. The number of positive patch test reactions decreased concomitantly with the decline of specific IgG. Histologically, eczematous changes were observed in the positive reaction sites. Many OA antigen-bearing Langerhans cells were found by the immuno-double labelling technique. Immuno-electron microscopic findings revealed the presence of OA antigens as well as IgG molecules on the cytoplasmic membranes of Langerhans cells. Our studies demonstrated that maternal sensitization with OA can induce an eczematous reaction in the newborns to OA patch testing under the presence of high levels of OA-specific IgG in the serum. From these findings it is suggested that IgG plays an essential role in the development of contact hypersensitivity reaction to OA.

Compression coating was investigated for use in preparing controlled release dosage forms having a polymer shell surrounding a soluble core. The purpose of the study was to develop a method of measure flux and permeability of water across the outer shell (coat) of the compression-coated tablet. One half of the shell of the press-coated tablets was mounted on the platform of the receptor port of the Thomas diffusion cell by embedment in white petrolatum. The cumulative amount of tritium labeled water per square centimeter permeating across the barrier was plotted vs time, and flux, lag time, diffusion coefficient and permeability were calculated from the steady-state slope. No difference was found whether the outside or inside of the membrane was exposed to the donor phase. The lag time increased linearily and significantly from 0.3 to 0.79 to 1.1 h with increasing shell thickness from 1.08 to 1.66 to 2.12 mm, respectively. Flux and permeability decrease hyperbolically with increasing shell thickness. Increasing hardness at constant shell amount significantly increases lag time and decreases flux and permeability. Compression-coating seems to be a viable technique for preparation of controlled release drug delivery systems with a wide range for adjustment of permeability.

Figure 2. Dermal lymphohistiocytic infiltrate with typical plasma cells (arrows). A 10-year old boy presented with a slowly growing (over 1 year) painless nodule on his left temple, pre-existing for 1 year (Figure 1). His general health was excellent; travel outside Germany was denied. The skin biopsy showed a diffuse granulomatous dermatitis mainly composed of epitheloid cells, and occasional multinucleated foreign body type giant cells. A granulomatous foreign body reaction after a ruptured epidermal cyst was diagnosed. After ineffective topical corticosteroid therapy, the first of a scheduled sequential excision was done. This specimen once more showed epitheloid granulomas now consuming the whole dermis. However, in contrast to the first biopsy, plasma cells were now spotted within the lymphohistiocytic infiltrate that prompted us to re-evaluate the diagnosis (Figure 2). Investigations for Borrelia and Mycobacteria were negative, but polymerase chain reaction revealed the presence of Leishmania donovani complex DNA. After confronting the patient and his mother with this result, the boy recalled a 2-week journey to a rural area near Barcelona, Spain, approximately 1 year before the skin lesion had occurred, thus, pointing at Leishmania infantum as the culprit infectious agent. Laboratory tests, clinical, and ultrasound investigations did not reveal any signs of systemic disease. Consequently, cutaneous leishmaniasis was diagnosed and topical 15% paromomycin/12% methylbenzethonium chloride in white petrolatum treatment under occlusion was initiated. After 2 months of treatment, the lesion completely resolved, leaving an atrophic scar.

VOLUME 87 NUMBER 6 remaining threads will serve to retain the acrylic resin and thus keep the coping in a fixed position). Place a small amount of utility wax (Kerr, Romulus, Mich.) in the abutment screw access hole to prevent the acrylic resin from flowing into it (Fig. 1). Leave the impression coping screw untightened so that the abutment screw can be loosened easily. 3. Lubricate the abutment and the conical abutment impression coping screw with petroleum jelly (White Petrolatum USP; E. Foguera and Co, Melville, N.Y.). 4. Place pattern resin around the abutment, keeping A customized guide for transferring angled abutments

REFERENCES 1. Sulzberger MB, Lazar MP. A study of the allergenic constituents of lanolin (wool fat). J Invest Dermatol 1950;15:453-8. 2. Guin JD. Eyelid dermatitis: experience in 203 cases. J Am Acad Dermatol 2002;47:755-65. 3. Green CM, Holden CR, Gawkrodger DJ. Contact allergy to topical medicaments becomes more common with advancing age: an age-stratified study. Contact Dermatitis 2007;56: 229-31. 4. Machet L, Couhe C, Perrinaud A, Hoarau C, Lorette G, Vaillant L. A high prevalence of sensitization still persists in leg ulcer patients: a retrospective series of 106 patients tested between 2001 and 2002 and a meta-analysis of 1975-2003 data. Br J Dermatol 2004;150:929-35. 5. Smack DP, Harrington AC, Dunn C, Howard RS, Szkutnik AJ, Krivda SJ, et al. Infection and allergy incidence in ambulatory surgery patients using white petrolatum vs bacitracin ointment. A randomized controlled trial. JAMA 1996;276:972-7.

Methods: Single center, activeand negative-controlled, investigator blinded, intra-individual comparison with randomized applications. The 4 products and the negative control were randomly applied on the upper area of the back under occlusive conditions. There were twelve 24-hour applications and three 72-hour applications on weekend during 3 weeks. A White Petrolatum site served as a negative control. Skin reactions (erythema score ,,b other local reaction) were assessed 15 to 30 minutes after removal of products. The Mean Cumulative Irritation Index (MCII) was calculated for each product by averaging individual CII’s across subjects.

Fifteen nonionic surfactants, 10% (w/w), were each incorporated into white petrolatum USP ointment base containing 10% (w/w) salicylic acid or 11.6% (w/w) sodium salicylate with 10% (w/w) dimethyl sulfoxide. Percutaneous absorption was determined from blood salicylate levels in New Zealand white rabbits at regular intervals for 8 hr following application of the ointment. Percutaneous absorption of salicylic acid was increased significantly when sorbitan monopalmitate, sorbitan trioleate, poloxamer 231, poloxamer 182, polyoxyethylene 4 lauryl ether, polyoxyethylene 2 oleyl ether, or polyoxyl 8 stearate was added to the ointment containing dimethyl sulfoxide, salicylic acid, and white petrolatum. Percutaneous absorption of sodium salicylate was increased significantly when sorbitan monolaurate, sorbitan monopalmitate, or poloxamer 182 was added to the ointment containing dimethyl sulfoxide, sodium salicylate, and white petrolatum.

A high-performance liquid chromatographic method for the prostaglandin E 1 (PGE 1 ) incorporated in white petrolatum, white ointment, hydrophilic petrolatum and Plastibase was investigated. The prostaglandin was separated from the oleaginous vehicles with n -hexane-aqueous acetonitrile. Most of white petrolatum, which is a principal component in the vehicles, remained in the n -hexane layer, and the recovery of the drug from any vehicle attained 100%. The method was applied to stability studies of PGE 1 in white petrolatum and macrogol ointment. In which pure PGE 1 and PGE 1 -α-cyclodextrin complex (PGE 1 -CD) were incorporated. The drug remained intact for up to 6 months when stored at 5°C. At 25 and 40°C, pure PGE 1 was more stable than PGE 1 —CD and both PGE 1 species were more stable in white petrolatum than in macrogol ointment.

Topical hypersensitivity to corticosteroids was studied by epicutaneous testing using the Finn Chamber technic. The steroids were tested in both ethanol and white petrolatum and, in certain cases, in dimethyl sulfoxide. Additionally, commercial preparations were tested. Three groups of patients were studied: (1) patients with a history of hypersensitivity to at least two topical preparations (five of ten patients studied showed a positive patch test reaction for corticosteroids), (2) patients in whom topical corticosteroid hypersensitivity was suspected because of treatment-resistant eczema (seven of twenty-five patients showed a positive patch test reaction), and (3) dermatologic inpatients and outpatients undergoing epicutaneous testing for suspected topical hypersensitivity. Hydrocortisone-17-butyrate (H-17-B) was included in the standard patch test series; of 450 patients tested, two showed a positive patch test reaction. All the patients with corticosteroid hypersensitivity had a positive reaction to H-17-B. In six patients, additional hypersensitivities to one or several other steroid preparations were seen. Use testing was performed as an open test, with 0.1% or 1% H-17-B in ethanol on normal skin of the flexor side of the upper extremities. A positive test reaction was seen in only one of nine patients. Results of use testing with the commercial 0.1% H-17-B (Locoid) ointment were always negative. Our study suggests that the sensitivity of patch tests for corticosteroid hypersensitivity can be increased by using ethanol as vehicle.

Ten percent polysorbate 85, a nonionic surfactant, was applied on the upper arm of 15 healthy individuals under occlusive dressing daily for 4 days. The other arm was similarly treated with the ointment base (white petrolatum USP) to provide the control area. At the end of treatment, macroscopic observations indicated minor erythema in 11 cases and no visible changes were noted on the surfactant-treated areas of 4 persons or any of the control areas. No definite histologic changes were observed by microscopic evaluations. The results of biochemical assays, however, were more definitive. The content of the epidermal phospholipids was elevated within a range of 5 to 65 percent as a result of the treatment with polysorbate 85 preparation. Radioactive tracer studies indicated higher rates of 32P incorporation into epidermal phospholipids, TCA-soluble, DNA and RNA fractions of the surfactant-treated skin. Results resemble those that were documented in earlier studies with rabbit skin.

Simplified methods for studying the release of drugs suspended in oleaginous ointment bases were developed. These procedures were used in studying the release rates of two corticoids, fluocinonide and flucloronide, from white petrolatum and petrolatum containing various adjuvants. A practical method for measuring drug solubilities was developed and used in determining solubilities of these corticoids in ointment bases. When using physical data obtained from model ointments, the release rates of drugs from modified ointment bases were predicted. Comparisons of the observed and predicted rates from ointments containing hydrophobic adjuvants indicated the usefulness of the physical model approach in predicting the release rates. For ointments containing emulsifying agents, the simple model used did not provide useful predictions.

Particle collections by paired rotoslide surfaces coated differentially with either of two silicone greases, white petrolatum or Lubriseal, were compared in two series of studies. Three samplers were employed, and adhesives were assigned randomly to the six available positions. Recovery differences were small but occasionally significant, with counts generally highest for silicone grease and lower with Lubriseal. During natural and simulated rainfall relative performances were similar, although differences were accentuated.

A Ferranti-Shirley cone and plate viscometer was utilized to characterize the spreading properties of white petrolatum U.S.P., white ointment U.S.P., and anhydrous lanolin U.S.P. Data were obtained for structural breakdown during repetitive cycling and for structural breakdown at constant shear. The problem of slippage at the revolving cone/sample interface is discussed. An attempt is made to relate rheological differences and molecular structure.

This report describes the use of heating-cooling curves for the study of polymorphism as it occurs in chemically pure or commercial samples of glyceryl mono-, di-, and tristearate, theobroma oil, spermaceti, white petrolatum, and cetyl alcohol. The interpretation of the data obtained by the heating-cooling method has been simplified by using a log temperature difference plot. With this plot, the usual temperature-time curve can be rationalized into a series of interconnecting straight lines. The effects of heating or cooling rates on crystal form and crystal transition temperatures were studied with the aid of the improved heating-cooling curve plots. Distinct polymorphic transitions were observed in the pure glyceryl stearates. On the other hand, in commercial materials there was little evidence that the observed crystal changes were associated with specific polymorphic transformations. The relationship between the transitions observed and the probable storage stability (i.e., the maintenance of film integrity, moisture permeability, etc.) is discussed.

Eight metallic soaps have been used to produce ointment bases by gelling the following vehicles: (a) white petrolatum, liquid petrolatum, anhydrous lanolin; (b) white petrolatum, liquid petrolatum, and (c) liquid petrolatum. The bases were studied at 8°, room temperature, and 45°. Penetration results indicate that gels of metallic soaps with heavy liquid petrolatum produced the most desirable preparations. Consistency changes were very slight over the above temperature extremes. These ointment bases are superior to white petrolatum both in thermo-stability and elegance. Anhydrous lanolin in these newly developed bases provides water-absorption capacity with no incompatibility. These new metallic soap gels proved to be superior or equal to other liquid petrolatum gels currently advocated as ointment bases. One hundred seventy-six ointments were prepared for compatibility observations. They represent eleven different medicaments tested with the various soap gels. A vast majority of the ointments prepared from metallic soap bases did not show the loss of homogeneity associated with white petrolatum base ointments. With the proper selection of the metallic soap gel ointment base, any of the eleven medicaments studied can be successfully compounded.

The site of action of surfactants incorporated in ointment bases was investigated with the aid of radioactive tracer techniques. Representative samples of the two major types of nonionic surfactants, polysorbate 85 and polyoxyethylene (10) oleyl ether were incorporated into white petrolatum and applied daily to rabbit skin clipped free of hair. After 4 days of treatment the excised epidermis was analyzed for phospholipids, nucleic acids, and the in vitro incorporation of 32P into phospholipids and the trichloroacetic acid (TCA)-soluble fractions. Results indicated that the surfactant treatment induced an increase in the epidermal phospholipid content, and a decrease in the phosphorus content of the TCA-soluble fraction. The incorporation of 32P into phospholipids and the TCA-soluble fraction was approximately 2-2.5 times greater in the surfactant-treated skin samples than in control samples. These and other available data suggest that the site of action of surface active agents is in the biological membranes. These surfactants may interact with membranes by either rupturing them, replacing certain phospholipids present in the lipid micelles, or inducing configurational changes in these micelles.

A semiquantitative method has been developed for measuring permeation of semi-solid materials by true diffusion. Adherence to theory has been demonstrated using aniline, nitrobenzene, and isovaleric acid as penetrants and white petrolatum and Jelene 1 as barriers. Application of this technique to the study of penetration of protective films by noxious chemicals gives an index to protective capacity.

The results of a study of the comparative absorption of radioactive sodium iodide from lard, wool fat, and petrolatum are reported, The results indicated that absorption of this salt was greater from white petrolatum than from either wool fat or lard. The white rat was used as the test animal.

Water, alcohol, and dimethyl sulfoxide were each incorporated at 1, 2, and 5 percent concentrations into four ointment bases containing salicylic acid. The bases tested were white petrolatum, a hydrogenated cottonseed oil base, a water-in-oil emulsion base and an oil-in-water base. The diffusion of salicylic acid from five samples of each mixture was determined at 20-min. intervals for a period of 2 hr. All three liquids enhanced diffusion from the white petrolatum base and the water-in-oil base but tended to inhibit diffusion from the cottonseed oil base and the oil-in-water formula. In some instances the concentration of liquid appears to have an effect. Statistical analyses of data point out significance of differences.

The triethanolammonium salts of dodecyl-, tetradecyl-, hexadecyl-, and octadecyl-sulfuric acids were prepared. Ointment bases were formulated from varying proportions of the salts, the corresponding alcohols, and propylene glycol. The release of salicylic acid, resorcinol, sulfadiazine, iodochlorhydroxyquin, and sulfur from these bases, polyethylene glycol ointment, and white petrolatum was studied by use of tissue digest procedures and microscopic examination, using guinea pigs as the test animals.

A hypothesis, namely, that the site of action of surfactants is in the biological membranes, was investigated with an indirect method. One representative member from each of 3 major types of nonionic surfactants was tested. Sorbitan trioleate, polysorbate 85, and polyoxyethylene ether 96 were incorporated, 10 percent in concentration, in white petrolatum and applied to rabbit skin daily. Measurements of lipid phosphorus indicated a considerable increase in the phospholipid content of the 0.1 mm. thick skin samples representing mainly the epidermis. Two reference standards were used: the wet weight and the deoxyribonucleic acid (DNA) content. After 4 days of treatment with polysorbate 85, sorbitan trioleate, and polyoxyethylene ether 96 preparations, the increase in phosphorus was found to be 23–56 percent, 28–73 percent, and 46–90 percent, respectively, on the basis of wet weight and 26–53 percent, 27–58 percent, and 47–81 percent, respectively, if DNA content was used as the reference standard. After 10 days of treatment, the increase in phosphorus was considerably smaller if calculated on the basis of DNA present in the sample, but did not differ much if wet weight was used as the reference. A comparison of the two reference standards demonstrated that the DNA content also increased after 10 days of treatment. The smaller spread in results indicated that DNA content may be more reliable as a reference standard, but the wet weight still can be used as a practical and useful standard of reference especially if the DNA content is also influenced by the test.

The effect of fluocinonide ointment and 5% crude coal tar on clearance of plaque-type psoriasis vulgaris by phototherapy was studied in 25 hospitalized patients using the bilateral comparison technique. All treated areas received ultraviolet radiation from Westinghouse fluorescent FS-40 bulbs (290-400 nm) in doses calculated to produce a minimal delayed erythema. The topically applied compounds (fluocinonide ointment, 5% Crude coal tar, white petrolatum) were applied individually or in combination. In nearly all comparisons clearance of psoriatic plaques was obtained after the same number of ultraviolet exposures, although many (8 of 14) of the areas treated with fluocinonide ointment had an accelerated early response. It thus appears that although the use of topical corticosteroids may enhance the early therapeutic response of psoriatic plaques it does not hasten the clearance of these plaques.

The release of sulfathiazole and salicylic acid from white petrolatum containing ethoxylated surfactants of varying ethylene oxide chain length was evaluated by the dialysis method. The rate of release of the drugs increased with the ethylene oxide number of the added surfactant.