Topical Gel Formulation Research Articles

Easy Access to Supramolecular Gels of the Nonsteroidal Anti-inflammatory Drug Diflunisal: Synthesis, Characterization, and Plausible Biomedical Applications.

By exploiting salt formation, a new series of primary ammonium monocarboxylate salts of a nonsteroidal anti-inflammatory drug, namely, diflunisal, was synthesized. The majority of the salts thus synthesized turned out to be good gelators of various solvents, including the solvents (e.g., methyl salicylate and pure water) typically used for topical gel formulation. Single-crystal X-ray diffraction studies of a few gelator and nongelator salts in the series revealed details of the hydrogen-bonding networks present in the salts. Furthermore, one such gelator salt, namely, the diflunisal salt of serinol, was found to be biocompatible (MTT assay), and its anti-inflammatory (PGE2 assay) response turned out to be as good as that of the parent drug, which is indicative of its potential in biomedical applications.

Development and characterization naproxen gel bearing eucalyptus oil for topical delivery

Aim: Eucalyptus oil-based naproxen loaded gel system was developed for topical application on to the scalp in order to avoid the disadvantages associated with the oral administration of naproxen. Materials and Methods: Eucalyptus oil, propylene glycol, and Carbopol P-934 were used with different ratios in an attempt to develop topical gel formulations of naproxen. Eucalyptus oil also has the property to reduce inflammation and arthritis pain. The tropical gel containing naproxen was evaluated for appearance, homogeneity, gelling, pH, viscosity, spreadability and drug content. In-vitro diffusion studies of prepared gel formulations were carried out in phosphate buffer pH 6.8 using Francz diffusion cell. Results: The results of in-vitro drug release showed that the highest release (99.37% of drug released after 3 h) was from in formulation F3 containing Carbopol P-934 (1%) and eucalyptus oil (0.6 ml). Conclusion: The overall results of this study suggest that the F3 formula could be used in the preparation of naproxen gel containing eucalyptus oil as a topical dosage form to be used in the treatment of inflammation.

In-vitro release and in-vivo performance of tolmetin from different topical gel formulations

This study was designed to evaluate the suitability of Pluronic F-127, different grades of Carbopol and cellulosic polymers as gel bases containing tolmetin, a non-steroidal anti-inflammatory drug. In vitro release characteristics, effect of enhancers, viscosity and the mechanism of drug release for different gel bases was studied as well as the anti-inflammatory activity were evaluated. The results showed that the HPMC gel has the superior percent of drug release than the others. The percent released of drug from Carbopol and the Pluronic F-127 gels is concentration defendants. It was found that the drug release from the tested gel bases obeyed the diffusion mechanism. The use of propylene glycol and urea in different concentrations (3.0, 5.0 and 10 % w/v) had enhanced the percent of drug release significantly (p < 0.05). The anti-inflammatory activity of the drug in Carbopol gel formulation showed excellent anti-inflammatory activity. These finding highlight the potential local application of tolmetin gel as topical anti-inflammatory medication.

Development and Characterization Naproxan Gel bearing Eucalyptus Oil for Topical Delivery

Aim: Eucalyptus oil based naproxen loaded gel system was developed for topical application on to the scalp in order to avoid the disadvantages associated with the oral administration of naproxen. Methods: Eucalyptus oil, propylene glycol and Carbopol P-934 were used with different ratios in an attempt to develop topical gel formulations of naproxen. Eucalyptus oil also has the property to reduce inflammation and arthritis pain. The tropical gel containing naproxan was evaluated for appearance, homogeneity, gelling, pH, viscosity, spreadability and drug content. In-vitro diffusion studies of prepared gel formulations were carried out in phosphate buffer pH 6.8 using Francz diffusion cell. Results: The results of in vitro drug release showed that the highest release (99.37% of drug released after 3 hr) was from in formulation F3 containing Carbopol P- 934 (1%) and Eucalyptus oil (0.6 ml). Conclusion: The overall results of this study suggest that the F3 formula could be used in the preparation of naproxen gel containing eucalyptus oil as a topical dosage form to be used in the treatment of inflammation.

A supramolecular topical gel derived from a non-steroidal anti-inflammatory drug, fenoprofen, is capable of treating skin inflammation in mice.

A new series of bioconjugates derived from a non-steroidal anti-inflammatory drug (NSAID), namely fenoprofen, has been synthesised by amidation with various biogenic molecules such as β-alanine, aminocaproic acid and tyramine with the aim of converting the NSAID into a supramolecular gelator for plausible biomedical applications. One such bioconjugate (2) showed gelation ability with methylsalicylate (MS) and 1% menthol in methyl salicylate (MMS) solvents. These gels were characterized by table top rheology, high resolution-transmission electron microscopy (HR-TEM) and dynamic rheology. Gelator 2 was found to be biostable both in proteolytic enzymes and in blood serum of BALB/c mouse under physiological conditions. It was also found to be biocompatible, as revealed by the methyl thiazolyldiphenyl tetrazolium bromide (MTT) assay in mouse macrophage RAW 264.7 and mouse myoblast C2C12 cells. The anti-inflammatory response (prostaglandin E2 assay, denoted PGE2 assay) of 2 was comparable to that of the parent drug fenoprofen calcium salt. Finally, a topical gel formulation of 2 displayed in vivo self-delivery application in treating imiquimod (IMQ) induced skin inflammation in BALB/c mice.

Influence of colloidal silicon dioxide on gel strength, robustness, and adhesive properties of diclofenac gel formulation for topical application.

The objective of this study is to identify the extent of stiffness, adhesiveness, and thixotropic character of a three-dimensional gel network of a 1% diclofenac sodium topical gel formulation in the presence and absence of colloidal silicon dioxide (CSD) and assess its ease of application and adhesiveness using both objective and subjective analysis. The 1% diclofenac gel was mixed with different amounts of CSD (e.g., 0.5, 1, 2, 3, and 5% w/w) and allowed to equilibrate prior to testing. The texture analyzer in combination with a cone-cap assembly was used to objectively investigate the changes in spreadability and adhesiveness of the gel system before and after addition of CSD. Results indicate that an increase in pliability and adhesiveness at levels ≥2 to ≤5% w/w of CSD dispersed in the gel ensues. For subjective analysis, gels with (2% w/w) CSD and in the absence of CSD were uniformly applied to a 20-cm(2) (5 cm × 4 cm) surface area on the forearms of healthy volunteers and vehicle preferences by the volunteers regarding ease of application, durability on the skin, compliance, and feelings concerning its textural properties were assessed. It appears that changes in the gel formulation with the addition of CSD enhance gel viscosity and bonding to the skin. Results further show that changes in physical and rheological characteristics of gel containing 2% w/w CSD did not significantly change subject preferences for the gel preparations. These findings may help formulators to have additional options to develop more robust and cost-effective formulations.

Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations

This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.

Novel Stability-Indicating RP-HPLC Method for the Simultaneous Estimation of Clindamycin Phosphate and Adapalene along with Preservatives in Topical Gel Formulations.

A novel stability-indicating RP-HPLC method was developed for the simultaneous estimation of clindamycin phosphate (hydrophilic), adapalene (hydro-phobic), phenoxyethanol, and methylparaben in topical gel formulations. Optimum chromatographic separation among the analytes and stress-induced degradants peaks was achieved on the XBridge C18 (50 × 4.6 mm, 3.5 µm) column using a mobile phase consisting of a variable mixture of pH 2.50 ammonium hydrogen phosphate buffer, acetonitrile, and tetrahydrofuran with gradient elution. Detection was performed at 210 nm for phenoxyethanol, methylparaben, and clindamycin phosphate and 321 nm for adapalene. The method was optimized with a unique diluent selection for the extraction of clindamycin phosphate and adapalene from the gel matrix. The developed method was validated for method precision, specificity, LOD and LOQ, linearity, accuracy, robustness, and solution stability as per ICH guidelines. The proposed method can be employed for the quantification of clindamycin phosphate, adapalene, phenoxyethanol, and methylparaben in commercial topical gel formulations.

Design expert assisted formulation of topical bioadhesive gel of sertaconazole nitrate.

The objective of this work was to develop a bioadhesive topical gel of sertaconazole nitrate with the help of response-surface approach. Experiments were performed according to a 3-level factorial design to evaluate the effects of two independent variables [amount of Carbapol 934 = X1) and Sodium carboxymethylcellulose (NaCMC) = X2)] on the bioadhesive character of gel, rheological property of gel (consistency index), and in-vitro drug release. The best model was selected to fit the data. Mathematical equation was generated by Design Expert® software for the model which assists in determining the effect of independent variables. Response surface plots were also generated by the software for analyzing effect of the independent variables on the response. The effect of formulation variables on the product characteristics can be easily predicted and precisely interpreted by using a 3-level factorial design and generated quadratic mathematical equations. On the basis of product characteristics viscosity, bioadhesiveness, permeation study, in-vitro release, in-vivo studies, TPA and spreadability it can be concluded that the best batch of topical bioadhesive gel of Sertaconazole nitrate would be with 1% Carbopol 934 and 1% NaCMC.

Designing Preclinical Perceptibility Measures to Evaluate Topical Vaginal Gel Formulations: Relating User Sensory Perceptions and Experiences to Formulation Properties

Abstract The effectiveness of any biomedical prevention technology relies on both biological efficacy and behavioral adherence. Microbicide trials have been hampered by low adherence, limiting the ability to draw meaningful conclusions about product effectiveness. Central to this problem may be an inadequate conceptualization of how product properties themselves impact user experience and adherence. Our goal is to expand the current microbicide development framework to include product "perceptibility," the objective measurement of user sensory perceptions (i.e., sensations) and experiences of formulation performance during use. For vaginal gels, a set of biophysical properties, including rheological properties and measures of spreading and retention, may critically impact user experiences. Project LINK sought to characterize the user experience in this regard, and to validate measures of user sensory perceptions and experiences (USPEs) using four prototype topical vaginal gel formulations designed for pericoital use. Perceptibility scales captured a range of USPEs during the product application process (five scales), ambulation after product insertion (six scales), and during sexual activity (eight scales). Comparative statistical analyses provided empirical support for hypothesized relationships between gel properties, spreading performance, and the user experience. Project LINK provides preliminary evidence for the utility of evaluating USPEs, introducing a paradigm shift in the field of microbicide formulation design. We propose that these user sensory perceptions and experiences initiate cognitive processes in users resulting in product choice and willingness-to-use. By understanding the impact of USPEs on that process, formulation development can optimize both drug delivery and adherence.

Formulation and evaluation of topical gel of aceclofenac

Topical gel formulations of Aceclofenac were prepared using these polymers such as Carbopol‐934, Carbopol‐941, HPMC, Poloxamer 407 in different concentration for the treatment of rheumatoid arthritis. The gels were evaluated for various parameters such as homogeneity, grittiness, skin irritancy, extrudability, in vitro drug release, viscosity(Brooke field viscometer), pH, drug content, stability studies. The in vitro release rate of gel was evaluated using Franz diffusion cell containing cellophane membrane with phosphate buffer pH 7.4 as the receptor medium. The release rate of the gel was found to obey Higuchi model. The percentage of drug release follow following order Poloxamer-407&gt; HPMC&gt; Carbopol-940&gt;Carbopol-934. Keywords: Aceclofenac, carbopol, poloxamer hydroxyl propyl methyl cellulose, anti inflammatory activity.

Hydroxychloroquine niosomes: A new trend in topical management of oral lichen planus

The work aimed at studying a novel topical niosomal gel formulation of hydroxychloroquine for the management of oral lichen planus. Niosomes have been reported as conceivable vesicles to deliver drug molecules to the desired mucous membrane or skin layers. Hydroxychloroquine niosomes were designed using different methods of preparation. Tween 20 and cholesterol in molar ratio (1:0.5) were used. The prepared systems were characterized for entrapment efficiency, particle size and in vitro drug release. Different factors affecting the encapsulation of hydroxychloroquine in niosomes were studied vs. varying the type of surfactant, the cholesterol:surfactant molar ratio and the amount of the drug. The selected noisome formulation was dispersed in different gel formulations and evaluated according to the in vitro drug release and the physical stability. The results showed that the type of surfactant, cholesterol ratio and incorporated amount of drug altered the entrapment efficiency and the in vitro release of hydroxychloroquine from niosomes. The optimum formulation was prepared by reverse phase evaporation technique using Brij 98:cholesterol molar ratio (1:1.5) and containing 20mg of hydroxychloroquine and incorporated in 20% w/v Pluronic F-127 gel. A double-blind, controlled clinical study was performed using two groups of patients. Group A (n=11) who received hydroxychloroquine niosomal gel formulation, one application-a-day over 4 months showed 64.28% reduction in the size of lesions and the average score of pain was reduced from "4" to "1". Compared to placebo group B (n=5), who showed only 3.94% reduction in the lesion size and the average score of pain was remained "3". Our results suggest that these niosomal formulations could constitute a promising approach for the topical treatment of oral lichen planus in short time with less side effects and no recurrence after stopping the treatment.

PREPARATION AND EVALUATION OF CARBOXYMETHYL ENSET AND CASSAVA STARCHES AS PHARMACEUTICAL GELLING AGENTS

Starch is usually modified either chemically, physically or enzymatically to augment its convenience for industrial use. In the current study, starches from Enset and cassava plants were carboxymethylated, and factors which affect the carboxymethylation process and degree of substitution (DS) were studied. The application of the carboxymethyl starches as alternative pharmaceutical gelling agents for topical delivery of drugs was also investigated. Accordingly, nine different topical gel formulations of ibuprofen were prepared. All formulations were evaluated with respect to cosmetic qualities, pH, drug content, viscosity, spreadability, extrudability, in vitro drug release, anti-inflammatory activity and stability. The results showed that carboxymethylation was significantly affected by the starch source, reaction medium, temperature and time. All ibuprofen gel formulations showed homogeneous appearance, smooth texture and pleasant odor. The pH values of the formulations ranged from 6.80 to 7.22. Ibuprofen content ranged between 98.76 and 100.20% ensuring the uniformity of the drug content. The cumulative percent ibuprofen released over 12 h across cellulose membrane ranged from 43.8% cm-2 to 84.5% cm-2. Spreadability, extrudability, the cumulative drug release and diffusion coefficient of ibuprofen were influenced not only by the rheological properties of the formulations but also by the nature of the modified starches. Physicochemically stable ibuprofen gels were obtained with potent anti-inflammatory activities. Â Keywords: Enset starch, cassava starch, carboxymethylation, degree of substitution, ibuprofen gel, in vitro drug release, anti-inflammatory activity, stability study

Chlorpromazine bioavailability from a topical gel formulation in volunteers

Symptom management medications are often compounded into topical gel formulations providing an alternative route of administration for hospice and palliative care patients. Though commonly used, transdermal absorption and bioavailability studies of these gel products are lacking. Chlorpromazine was studied because it is FDA approved for treatment of nausea and vomiting and is used off-label for treatment of agitation and delirium. The objective of this study is to determine the transdermal absorption of chlorpromazine PLO gel in healthy adults. Twenty-five milligrams of chlorpromazine in PLO gel was applied to 10 subjects' wrists and 100 mg was applied to 1 subject's wrist. Blood draws were completed preapplication and 1, 2, and 4 hours postapplication. This single-center unblinded study recruited healthy adults between 18 and 70 years of age. Participants were not pregnant, did not have an allergy to any component of the study medication, and were not taking a phenothiazine medication. Chlorpromazine was undetected in any of the 11 subjects' blood samples. There is an assumption of equivalent medication absorption in healthy patients and palliative care or hospice patients. Rapid relief of symptoms at end of life is essential. Chlorpromazine in PLO gel may not be an effective treatment option since blood levels were undetectable at 1, 2, and 4 hours after topical application.

ANTIACNE EFFECT OF POLYHERBAL GEL FORMULATION IN MALE SPRAGUE-DAWLEY RATS

Acne vulgaris is the common est skin disorder to affect humans, characterized by both non - inflammatory (comedones) and inflammatory lesions (papules, pustules, and nodulocystic lesions). Topical gel formulation has been developed containing Barleria prionitis, Butea monosperma, Casua rina equisetifolia, Dalbergia sissoo and Lagenaria siceraria . In vivo antiacne activity was performed for the formulation s using male sprague dawley rats. Physical observations were carried out at regular intervals on the ra t ear and progressive fa ding of comedo was found on treated animals . T est group show ed significant improvement on comedo reduction of rat pinna observed photographically. Test group showed a significant i mprovement compared to standard . The presen t study scientifically evaluates the anti acne potential of the herbs as a single entity as well as i n combination using in vivo methods. The results obtained will help in identification and isolation of bioactive constituents for treating the ro ot causes

Formulation and evaluation of antipsoriatic gel using natural excipients

ObjectiveTo develop topical gel formulations of Psoralen using natural excipients to minimize the side effects of synthetic drugs. MethodsThe Psoralen gel formulations were prepared using different natural gums and polymers. The physicochemical compatibility between Psoralen and other excipients was confirmed by using Fourier transform infrared spectroscopy. All prepared gel formulations were evaluated for drug content uniformity, viscosity, pH, and stability. The release of psoralen from all formulations using dialysis membrane into a phosphate buffer pH 6.8 at 37°C was studied. Drug release from the formulations fitted best to the Higuchi model. From the drug release data the best formulation was optimized and the biological studies on albino mice were performed. ResultsPsoralen gel containing egg albumin and xanthan gum shows better incorporation of the drug. The drug activity was found to be 43.3%. Anti-psoriatic drug enhances the orthokeratotic cell differentiation in the epidermal scales. ConclusionsIn vitro anti-psoriatic activity of F3 showed the significant orthokeratosis in the mouse tail test when compared to control thus indicating that the formulation is effective in treating psoriasis.

A multi-centre, blinded, randomised, placebo-controlled, laboratory-based study of MQX-503, a novel topical gel formulation of nitroglycerine, in patients with Raynaud phenomenon

ObjectiveMQX-503 is a novel nitroglycerine preparation designed to absorb quickly and allow local vasodilatation in the skin. We examined the efficacy and tolerability of this medication in Raynaud phenomenon (RP)...

A Novel Botulinum Neurotoxin Topical Gel: Treatment of Allergic Rhinitis in Rats and Comparative Safety Profile

Rhinitis affects a significant proportion of adults and children with typically seasonal or chronic symptoms. Botulinum neurotoxin type A (BoNTA) is a well-known cholinergic antagonist widely used in a number of approved neurological and esthetic indications. This study was designed to assess the therapeutic effect of RT001, a novel topical gel formulation of BoNTA, in the treatment of allergic rhinitis using a rat model and to compare its safety profile with that of an aqueous formulation of BoNTA complex. A rat model of allergic rhinitis was used involving induction of classic rhinitis signs (sneezing and nasal itch) in addition to nasal inflammatory pathology to assess the degree of therapeutic effect of RT001. Comparative safety of RT001 and BoNTA complex was assessed in guinea pigs based on lethality and body weight gain. Clinical signs of rhinitis were significantly (p < 0.01) relieved after a single intranasal administration of RT001 and resolved to normal baseline levels within 5 days after treatment. Mucosal inflammation characterized by edema, congestion, and vascular dilatation along with increased expression of vasoactive intestinal peptide was noted in control animals after allergy induction, whereas RT001 treatment resolved inflammation to essentially normal baseline levels. Safety studies in guinea pigs via intranasal dosing revealed ∼31-fold greater safety factor for RT001 when compared with BoNTA complex. These results suggest that topical intranasal application of RT001 is effective in relief of clinical signs and inflammatory pathology associated with allergic rhinitis in a rodent model and may provide a safe treatment for rhinitis.

Ethogel topical formulation for increasing the local bioavailability of 5-fluorouracil

5-Fluorouracil (5-FU) is an anticancer drug and is considered a gold standard for the treatment of skin cancer. At present, topical chemotherapy with 5-FU is associated with the limitations of poor skin permeation, retention at target site, and skin irritation potential. In the present study, an attempt has been made to develop an ethosome-based topical gel formulation (ethogel) for skin targeting of 5-FU. The ethosomal formulation was prepared using the classical dispersion method, and loading of 5% w/w of the drug was optimized to the commercial strength of marketed 5-FU cream. Carbopol 934P was used as a gel former in 0.5, 0.75, 1.0, and 1.5% w/w concentration for preparation of ethosome-based ethogel formulation. The ethogel formulation was characterized for viscosity, spreadability, extrudability, and pH. Viscosity of the developed ethogel and that of the marketed formulation was found to be 3070±14.7 and 2870±14.4 cP, respectively. An in-vitro skin permeation and deposition study was carried out across rat skin using the marketed cream and 5-FU drug solution as controls. The amount of drug deposition was found to increase 5.9- and 9.4-fold on treatment with ethogel in comparison with the marketed cream and drug solution, respectively. The result of antitumor activity evaluated using a Cytoselect 96-well cell transformation assay revealed a large reduction in tumor density with treatment with the 5-FU ethogel formulation in comparison with the marketed formulation. A significant reduction in the skin irritation potential of 5-FU ethogel formulation was also found in comparison with that of the marketed formulation as measured by the Draize test. The results of the present study demonstrated ethogel as a better alternative for increasing the local bioavailability of 5-FU in comparison to the marketed formulation.

Submicron Size Formulation of Linseed Oil Containing Omega-3 Fatty Acid for Topical Delivery

The aim of the present study was to design and develop topical submicron size gel formulation of linseed oil with enhanced permeation through the skin for the management of psoriasis. Linseed oil contains significant amount of α-linolenic acid (ALA) an omega-3 fatty acid, which is responsible for its pharmacological actions. In order to enhance permeation through skin, microemulsion based gel formulation was prepared and characterized. Microemulsions were prepared by aqueous phase titration method, using linseed oil, Unitop 100, PEG 400, and distilled water as the oil phase, surfactant, cosurfactant and aqueous phase, respectively. Selected formulations were subjected to physical stability studies and consequently in vitro skin permeation studies. Surface morphology studies of optimized formulation were done by transmission electron microscopy (TEM). The droplet size of microemulsions ranged from 70 to 500 nm with average particle size 186 nm. The optimized microemulsion was converted into hydrogel using carbopol 971 which had a viscosity of 498 ± 0.04 cps. During in vitro permeation study the flux of microemulsion formulation and gel was found to be 19.05 and 10.2 µg/cm2/hr, respectively, which indicated better penetration of linseed oil through the skin. These result indicated that the developed ME formulation may be a good approach for topical therapy for the management of psoriasis.