Compounded gabapentin for neuropathic pain: Stability and beyond-use date (BUD) in some commonly used bases.

OBJECTIVES: To investigate the stability and beyond-use date (BUD) of topical gabapentin in 3 commonly used bases. METHODS: Lipoderm cream, Versabase gel, and Emollient cream were used to compound gabapentin (10%). The products were stored in Ecolojars, kept at 25°C, 4°C, and 40°C, and samples were collected on different days (days 0, 14, 28, and 90). Potency, stability, and organoleptic changes were monitored. RESULTS: At 25°C and 40°C, the potency of gabapentin in Lipoderm cream significantly increased (P < 0.05) after 28 and 90 days, respectively. In contrast, gabapentin degraded in Emollient cream (P < 0.05). At 25°C, the organoleptic properties of the drug compounded with Lipoderm cream (25°C) remained consistent for up to 28 days but showed signs of physical changes in other bases. Gabapentin recrystallized from Versabase gel and Emollient cream within 14 days. CONCLUSION: Gabapentin compounded with Lipoderm cream for topical use was stable in Ecolojars for 28 days at 25°C. Under the same conditions, the drug was not stable in Versabase gel and Emollient cream. Based on our stability and potency data, the beyond-use date of currently dispensed gabapentin (10%) formulations with Lipoderm cream should not be extended beyond the currently assigned 30-day mark, even when refrigerated. It is unclear whether the stability of these formulations is improved if stored in air-tight containers.

Physical and Chemical Stability of Estriol 0.025% to 1% Vaginal Creams (VersaBase).

Estrogen replacement therapy is often recommended when female patients present with lower than normal physiologic levels, such as patients going through menopause. The physical and chemical stability of estriol 0.25 mg/g and 10 mg/g vaginal creams (VersaBase) was tested over a period of 182 days, at room temperature and refrigerated conditions, in order to determine the corresponding beyond-use date. The physical characterization consisted in observing all samples for color/appearance and odor, and testing for pH, whereas the chemical characterization consisted in ultra-performance liquid chromatography assay testing. Both vaginal creams were proven physically and chemically stable, and the ultra-performance liquid chromatography method was proven stability indicating. As a result, the beyond-use date of the estriol 0.025% to 1% vaginal creams (VersaBase), in electronic mortar and pestle plastic jars, is six months at both room temperature and refrigerated conditions.

Molecular self-assembly of copolymer from renewable phenols: new class of antimicrobial ointment base.

Ointments are highly viscous forms intended for external applications either medicated or non-medicated means. Formulation of ointment depends upon the base ingredients to measure the viscosity difference. Several limitations of ointment bases has been encountered timely as agglomeration, oil phase ingredients can form lumps, poor dispersion, poor drug delivery efficiency, make stained, immiscible, and difficult to wash off. Therefore, it is necessary to make a new type of ointment bases that can overcome those limitations. This review summarizes a new type of ointment base preparation from the copolymer of renewable phenolic derivatives. The nanohydrogel preparation from these copolymers are especially effortless and highly efficient in drug delivery, exhibited versatile biological activities such as antioxidant, anti-inflammatory and wound healing in addition to antimicrobial property. Molecular self-assembly mechanisms have been addressed for nanogel formulation. The strategy makes a significant value in health-care application and be supposed to come marketed soon.

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.

Eucerin: A Revolutionary Formulation Still Going Strong for Over a Century.

Eucerit, now more commonly known as Eucerin, was a revolutionary emulsion developed more than 100 years ago that is still popular and in common use today. The initial formulation is still the basis for a relevant global product line that holds significant market share today. The concept for Eucerin was originally developed in Germany by Dr Isaac Lifschütz, who helped develop Eucerin, meaning "beautiful wax," in 1898. The ointment was very smooth, allowing Eucerin to develop as a stable emulsion. Eucerin was revolutionary and outperformed all of its predecessors in emulsion stability, moisturizing ability, its ability to resist degradation, and its cost-effectiveness.1.

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.

Clinical effect of four different ointment bases on healthy cat eyes.

OBJECTIVE: To describe the effects of long-term treatment with four different eye ointment bases (OBs) in cats. ANIMALS STUDIED: Ten healthy cats. PROCEDURES: The study was performed in two periods. Four different OBs were tested. Hundred grams of OB contained the following: OB-A: 35.17 g liquid paraffin (lp), 64.83 g white petrolatum (wp); OB-B: 10.03 g lp, 84.95 g wp 5.02 g lanolin; OB-C: 18.34 g lp, 51.40 g wp, 25.00 mg KH2 PO4 , 57.00 mg K2 HPO4 , 18.90 g eucerinum anhydricum, 11.28 g water for injections; and OB-D: 70 g unguentum lanalcoli, 20 g lp, 10 g aqua conservans. One eye was treated, and the other served as a negative control. Cats received the OBs TID for 28 days. The two study periods were separated by a 4-month washout phase. Samples for conjunctival impression cytology, swabs for bacteriologic and mycologic examination, and cytobrush samples for FHV-1 and Chlamydophila felis PCR detection were obtained. Both eyes were examined daily. Severity of ocular symptoms was scored using a modified Draize eye irritation test. A total of five eyes were treated with OB-A, five with OB-B, four with OB-C, and five with OB-D. RESULTS: Treated eyes had significantly higher clinical scores. Eyes receiving OB-A had the highest overall clinical score. The results of bacteriologic and mycologic examination concur with the previously published data. All samples tested were negative for FHV-1 and Chlamydophila felis. There was no significant difference between treated and control eyes upon cytological examination. CONCLUSION: The application of OBs resulted in clinical symptoms in treated eyes. The long-term use of ointments is not well tolerated in cats and may lead to ocular irritation.

Kinetics of drug release from ointments: Role of transient-boundary layer.

In the current work, an in vitro release testing method suitable for ointment formulations was developed using acyclovir as a model drug. Release studies were carried out using enhancer cells on acyclovir ointments prepared with oleaginous, absorption, and water-soluble bases. Kinetics and mechanism of drug release was found to be highly dependent on the type of ointment bases. In oleaginous bases, drug release followed a unique logarithmic-time dependent profile; in both absorption and water-soluble bases, drug release exhibited linearity with respect to square root of time (Higuchi model) albeit differences in the overall release profile. To help understand the underlying cause of logarithmic-time dependency of drug release, a novel transient-boundary hypothesis was proposed, verified, and compared to Higuchi theory. Furthermore, impact of drug solubility (under various pH conditions) and temperature on drug release were assessed. Additionally, conditions under which deviations from logarithmic-time drug release kinetics occur were determined using in situ UV fiber-optics. Overall, the results suggest that for oleaginous ointments containing dispersed drug particles, kinetics and mechanism of drug release is controlled by expansion of transient boundary layer, and drug release increases linearly with respect to logarithmic time.

Microencapsulation of citronella oil for mosquito-repellent application: formulation and in vitro permeation studies.

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.

Comparison of physical properties and drug-releasing characteristics of white petrolatums.

White petrolatums of Japanese Pharmacopoeia grade and Sun white marketed as a cosmetic were characterized by measuring their physical properties and drug-releasing characteristics. White petrolatums of Japanese Pharmacopoeia grade available commercially in Japan were Perfecta, White 1S, Ultima, Snow, Snow V and Regent (Propeto). Penetrating stress, shear stress and spreading properties were measured as physical properties of the white petrolatums. The physical properties of white petrolatums varied, and Regent was the softest and the most spreadable ointment base. In vitro release test was performed using flow-through Franz diffusion cells. Fluorescein isothiocyanate and tetracycline hydrochloride were used as drug models. Their release characteristics varied among the tested white petrolatums, and Regent had the best release properties. Among the white petrolatums, with the exception of Regent, the release properties should depend on the distribution of drugs between white petrolatum and the receiver solution. Considerations of usability and characteristics of theprincipal agent are needed when choosing white petrolatums.

Rheological evaluation of petroleum jelly as a base material in ointment and cream formulations: steady shear flow behavior.

The objective of the present study is to systematically characterize a nonlinear rheological behavior of petroleum jelly (petrolatum) in steady shear flow fields correspondent to the spreading condition onto the human body. With this aim, using a strain-controlled rheometer, the steady shear flow properties of commercially available petroleum jelly have been measured at 37 degrees C (body temperature) over a wide range of shear rates. In this article, the shear rate dependence of steady shear flow behavior was reported from the experimentally obtained data. In particular, the existence of a yield stress and a non-Newtonian flow behavior were discussed in depth with a special emphasis on their importance in actual application onto the human body. In addition, several inelastic-viscoplastic flow models including a yield stress parameter were employed to make a quantitative description of the steady shear flow behavior, and then the applicability of these models was examined in detail. Main findings obtained from this study can be summarized as follows: (1) Petroleum jelly exhibits a finite magnitude of yield stress. The appearance of a yield stress is attributed to its three-dimensional network structure that can show a resistance to flow and plays an important role in determining a storage stability and sensory feature of the product. (2) Petroleum jelly demonstrates a pronounced non-Newtonian shear-thinning flow behavior which is well described by a power-law equation and may be interpreted by the disruption of a crystalline network under the influence of mechanical shear deformation. This rheological feature enhances sensory qualities of pharmaceutical and cosmetic products in which petroleum jelly is used as a base material during their actual usage. (3) The Casson, Mizrahi-Berk, Heinz-Casson and Herschel-Bulkley models are all applicable and have almost an equivalent ability to quantitatively describe the steady shear flow behavior of petroleum jelly whereas the Bingham model does not give a good validity. Among these flow models, the Herschel-Bulkley model provides the best applicability.

Improving rheological characteristics of hydrophilic ointment base by treatment with a high-pressure wet-type jet mill.

BACKGROUND: A high-pressure wet-type jet mill is a powerful equipment used for the dispersion and emulsification of substances. In this study, we investigated its usefulness in the preparation of skin cream formulations. METHOD: We prepared a hydrophilic ointment base as a typical skin cream base, and then treated it with the wet-type jet mill under different conditions. Controllable factors of the wet-type jet mill included processing pressure, treatment cycle, and temperature of the treatment. RESULT: Treatment with the wet-type jet mill had a great impact on the rheological characteristics of the hydrophilic ointment base. The hysteresis areas and yield values of the treated ointments were significantly increased by increasing the processing pressure and temperature during the treatment. From scanning electron microscopic observations, the oil droplet size of the hydrophilic ointments decreased after treatment with the wet-type jet mill, suggesting that a decrease in oil droplet size mediates changes in the rheological characteristics. CONCLUSION: Because we can expect the wet-type jet mill to control the rheological characteristics of the ointment, it is a promising tool for the preparation of skin cream formulations.

Why does a hydrophilic drug permeate skin, although it is not soluble in white petrolatum?

BACKGROUND: White petrolatum is broadly used as an ointment vehicle, although hydrophilic drugs cannot be easily dissolved in the vehicle. METHOD: The aim of this study was to evaluate the release and skin permeation profiles of a model hydrophilic agent, N1-[2-(4-guanidinophenyl)-1(S)-(N-methylcarbamoyl)ethyl]-N4-hydroxy-2(R)-iso-butyl-3(S)-(3-phenylpropyl)succinamide hydrochloride (FYK-1388b), from the ointment. RESULTS: The release rate of FYK-1388b was very low; however, high skin permeation and skin content of the drug were found. We supposed that this was due to endogenous lipids or sebum, because white petrolatum had a high affinity to these lipids. To evaluate the effect of lipids on the enhanced release and skin permeation of FYK-1388b, 'preapplied white petrolatum' was made by applying the drug-free white petrolatum on the hairless rat skin for 6 hours. Then the drug ointment was prepared using the 'preapplied white petrolatum'. The release rate of FYK-1388b was markedly increased from the 'preapplied ointment' compared with the 'original ointment'. In addition, much higher skin permeation was also obtained using the 'preapplied ointment'. Separately, cholesteryl oleate, cholesterol, and ceramides were found in the 'preapplied white petrolatum'. CONCLUSION: Thus, these endogenous lipids on the skin surface may enhance the release and skin permeation of FYK-1388b from white petrolatum ointment.

Viscosity of pharmacopeial multimolecular ointment vehicles and pharmaceutical availability of a model therapeutic agent.

Viscosity was tested of basic ointment vehicles such as: white petrolatum, yellow petrolatum, anhydrous lanolin and eucerin produced by different manufacturers. Ointment vehicles of definite type differ significantly in rheological parameters. In the same group of products, the experimentally determined viscosity value of some vehicles is two-fold (petrolatum, anhydrous lanolin) or even three-fold (eucerin) higher than that of others. On the basis of rheological tests, using Einstein-Smoluchowski equation (D = kT/ 6pireta), theoretical coefficient was calculated of a model therapeutic agent--salicylic acid diffusion (-log chi2(i) = 1,22) from the tested vehicles to the external compartment. The obtained results were related to the performed in vitro measurements of the rate of salicylic acid release from the above mentioned ointment vehicles to model acceptor fluid. High correlation was observed between theoretical values of diffusion coefficients calculated on the basis of viscosity measurements and tested experimentally pharmaceutical availability of salicylic acid. It was confirmed by describing this dependence with regression equations of high correlation coefficients (r > or = 0,9667). Marked disproportions between rheological parameters of the vehicles of definite type produced by individual manufacturers are the cause of differences in pharmaceutical availability of therapeutic agents contained in these vehicles.

Investigation on the photostability of tretinoin in creams.

In this investigation, the photodegradation of some tretinoin cream formulations was evaluated. Several oils were selected to prepare the cream formulations: olive oil, maize oil, castor oil, isopropyl myristate and Miglyol 812. A solubility study showed that tretinoin is best soluble in castor oil (0.60g/100ml), followed by isopropyl myristate, maize oil, Miglyol 812 and olive oil, respectively, 0.35, 0.30, 0.29 and 0.22g/100ml. The photostability of tretinoin in oils is comparable with the photostability of a tretinoin lotion (ethanol/propylene glycol 50/50), castor oil and olive oil giving slightly better results than the other oils. Investigation of the photodegradation of tretinoin in o/w creams, prepared with the same oils as mentioned above, revealed that tretinoin is far more stable in the cream formulations than in the respective oils, however it is not clear whether this is due to the formulation or due to a different irradiation technique. Tretinoin seemed to be most stable in the olive oil cream, followed by the castor oil cream. However microscopic investigation revealed the presence of tretinoin crystals in the olive oil cream, while the other creams were free of it. As a conclusion, one can say that the cream prepared with castor oil seems to be the most suitable one, in terms of solubility of tretinoin and in terms of photostability.

Effect of simultaneous insertion of oleaginous base on the absorption and on the anticonvulsant effect of diazepam suppository.

To clarify the drug-base interaction between diazepam (DZP) suppository and oleaginous base, we investigated the effect of simultaneous combination of oleaginous base on the absorption and on the anticonvulsant effect of DZP Suppository in rats. Simultaneous insertion of DZP suppository and oleaginous base significantly decreased maximum concentration (C(max)) and area under the blood concentration-time curve (AUC) of plasma DZP concentrations. Administration of DZP suppositories (2.5, 5 mg/kg) dose-dependently suppressed the pentylenetetrazol (PTZ)-induced seizures, and the anticonvulsant effect of DZP suppository (5 mg/kg) was reduced by simultaneous insertion of oleaginous base. In an in vitro study using a suppository release apparatus, simultaneous combination of DZP suppository and oleaginous base (1.5-98 mg) significantly decreased the accumulative release of DZP in a dose-dependent manner. These results suggested that when DZP suppository and oleaginous base are inserted simultaneously, the released DZP distributes partially to the oleaginous base, and this phenomenon is related to the decreases in the plasma concentration and the anticonvulsant effect of DZP.

Late opacification of a silicone intraocular lens caused by ophthalmic ointment.

A 55-year-old man had uneventful phacoemulsification with implantation of a 3-piece silicone intraocular lens (IOL). Postoperative medications included antibiotic-steroid drops and ointments. Eight months postoperatively, the patient started having recurrent episodes of anterior chamber inflammatory reaction. Suspicion that lens instability was causing the reactions led to a lens repositioning procedure 11 months after the initial surgical implantation and again at 13 months. Eighteen months postoperatively, the IOL had a "greasy" film. Despite antiinflammatory and antibiotic treatment, the clinical outcome did not improve. Twenty-seven months after implantation, the lens was exchanged with a hydrophilic acrylic IOL. The course after the exchange was uneventful. The explanted lens was examined by gross and microscopic evaluations, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and gas chromatography-mass spectrometry (GC-MS) using electronic ionization. Gross and microscopic evaluations confirmed the presence of a thin, oily film covering the IOL optic surface. Surface analyses at the level of the oily substance showed unspecific peaks of sodium, chloride, and potassium. The GC-MS analysis showed the presence of compounds characteristic of hydrocarbons, including docosane, tricosane, and tetracosane, which are commonly found in the vehicle of ophthalmic ointments. The GC-MS analysis of 1 ointment used postoperatively found matching peaks, suggesting deposition of those compounds on the IOL.

[Application of photochemically activated ointment based on polyethylene oxides for treatment of peritonitis].

There was given evidence, using the complex of morphological, morphometrical, biochemical and microbiological investigations in experiment, of the peritonitis treatment efficacy applying photochemically activated laevomecol ointment. The experiment was performed in 120 adult male white mongrel rats, following the recommendations of Vancouver's convention for biomedical investigations.

[Influence of the base on the release of antibiotics from ointments].

BACKGROUND: Officinal basis for the antibiotic ointments according to the 4th Yugoslav Pharmacopoeia is a hydrophobic base containing only aliphatic hydrocarbons. The fact that antibiotics are predominantly not lipophylic raises the question about the suitability of that particular type of the base for the manufacturing of antibiotic ointments. Recent studies of the lipid analysis of the skin corneal layer indicated that lipids had shown the bilamellar organization in the skin intercorneal space. Such structural organization could be seen in the ambiphylic bases whose structure was based on carefully selected emulsifier couple, consisting of the lyotropic and thermotropic liquid crystals. The aim of this study was to test the velocity of antibiotics (klindamycin hydrochloride, erythromycin base and chloramphenicol) release from the hydrophobic ointment-type bases, and from ambiphylic bases of anionic and non-ionic types. METHODS: Membrane-free agar diffusion test as the basic method for testing the release velocity in vitro and Staphylococcus aureus as the strain highly susceptible to the chosen antibiotics were used. All the analyzed samples were manufactured as the suspension-type ointments. RESULTS: The highest growth inhibition zone of the Staphylococcus aureus strain for all three analyzed antibiotics was achieved from the non-ionogenic ambiphylic base; the clear growth inhibition zone area for Staphylococcus aureus strain in the preparations containing anionic ambiphylic base was smaller by 10-31.28%, and in the preparations containing aliphatic hydrocarbon-type base, the decrease was 11.46 - 31.28%, compared to the results achieved with the non-ionogenic ambiphylic base. CONCLUSION: The optimal release velocity for the analyzed antibiotics was achieved from the non-ionic ambiphylic base.