PLO Gel Research Articles

Relieving postherpetic neuralgia pain via gabapentin-loaded bigels as an auspicious topical drug delivery system.

Over the past decades, a substantial portion of the population worldwide has been infected with varicella zoster and most cases developed shingles. Unfortunately, shingles is usually accompanied by postherpetic neuralgia, which may persist for months to years after the resolution of the viral infection. Gabapentin is an orallygamma-aminobutyric acid analogue approved by the Food and Drug Administration to manage shingles postherpetic neuralgia. However, gabapentin shows nonlinear pharmacokinetics, with variable absorption and bioavailability along with its short half-life and long side effects that may include dizziness and somnolence, which calls for an appropriate topical dosage form. Bigels are unique semisolid dosage forms with boosted penetrability and satisfactory hydrophilic texture. The current work pointed to formulating gabapentin-loaded bigels for the treatment of postherpetic neuralgia, where the analysis and optimization of design were performed via Design-Expert®. The selected bigel (F5), incorporating 400mg Span 60, 1000mg Tween 80, and 1000mg Transcutol, displayed spherical nanosized particles with acceptable viscosity and spreadability. Subsequent topical application of the selected bigel on the skin of Wistar rats, F5, demonstrated a boosted accumulation of gabapentin in the skin similar to PLO gel but superior to the drug solution. Furthermore, a histopathological study demonstrated the biosafety of the selected bigel when applied topically. Accordingly, gabapentin-loaded bigel would be considered a potentially topical dosage form for the delivery of gabapentin for the management of postherpetic neuralgia.

Percutaneous absorption and Skin accumulation of Lorazepam-Diphenhydramine- Haloperidol Carbopol gel in Porcine Ear Skin.

This study presents the formulation and evaluation of an ABH Carbopol gel containing lorazepam (Ativan®), diphenhydramine hydrochloride (Benadryl®), and haloperidol (Haldol®) for treating chemotherapy-induced nausea and vomiting (CINV) in hospice patients. ABH PLO gel is widely used for this purpose due to its low cost and presumed efficacy. However, previous studies, including one conducted by the authors, have reported insufficient drug absorption from the ABH PLO gel. Here we hypothesized that the ABH Carbopol gel would provide superior percutaneous absorption of the drugs. ABH Carbopol gel was characterized for pH, viscosity, thermal properties, and infrared spectroscopy. The percutaneous absorption and skin retention of the gel was evaluated across porcine ear skin using Franz diffusion cells, and the drug concentrations were determined by high-performance liquid chromatography. The pH of the ABH Carbopol gel was found to be 6.80 ± 0.33, and the retention time of diphenhydramine, haloperidol, and lorazepam were 4.73, 7.11, and 18.69 minutes, respectively. The thermogram of the ABH Carbopol gel indicates the drugs were present in the dissolved state. Based on the flux data, the estimated steady-state concentration (Css) of diphenhydramine, haloperidol, and lorazepam were found to be 44.64 ng/ml, 2.58 ng/ml, and 20.1 ng/ml, respectively. These values were significantly higher than those obtained from the ABH PLO gel. In conclusion, the ABH Carbopol gel provides a promising alternative to the ABH PLO gel for treating CINV in hospice patients. Further studies are required to validate these findings in clinical settings.

Formulation and evaluation of a novel controlled release mefenamic acid pluronic lecithin organogel

Based on pluronic lecithin, PLO gels were established in the present research as a topical carrier for the regulated delivery of mefenamic acid. To explore various factors utilizing In vitro diffusion experiments and in vivo study, ten organized formulations have been created using such methods that used lecithin as a lipophilic phase as well as pluronic F-127 as a hydrophilic phase in variable proportions. The pH values of all formulations were found to be between 5.60 and 5.75, which is nonirritating, and to be off-white, homogeneous, and unwilling to wash off easily. In formulations F1 to F5 (lecithin) but also F6 to F10 (pluronic), an increase in polymer concentration led to a drop in gelation temperature, an increase in viscosity, as well as a reduction within the spreadability of gels with a tendency for polymers to form rigid 3D networks. Higher viscosity organogels have been proven to be more stable and delay drug release from the gel. The formulations of F2 and F3 have been chosen for kinetic tests and stability studies because they had the most significant percentage of drug content and the highest drug release during eight hours, and all physical parameters were found to be within acceptable limits. It was discovered that the order of drug release through different formulations was F1to F10. A drug is removed from the improved formulation F2 in a regulated manner according to zero-order rate kinetics. The optimized mefenamic acid organogel (F2) in vivo anti-inflammatory effectiveness against a commonly used commercial product (Volini gel) was determined to be satisfactory but also significant.

Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice.

In clinical practice, pregabalin is orally administered for neuropathic pain, but causes severe central nervous system side effects, such as dizziness, which results in dose limitation or discontinuation. To reduce the central side effects of pregabalin, we developed four pregabalin preparations for transdermal application: 0.4% aqueous solution, pluronic lecithin organogel (PLO gel), hydrophilic cream, and lipophilic cream. Transdermal permeabilities of pregabalin among the four formulations were compared in vitro using hairless mouse skin. The longitudinal distribution of pregabalin within the skin was analyzed using mass spectrometric (MS) imaging. Furthermore, the in vivo analgesic effects of the formulations were evaluated using the von Frey filament test in a mouse model of diabetic neuropathy (DN). The PLO gel showed the highest permeability of pregabalin, followed by the aqueous solution, and no permeation was observed in the two cream formulations. The MS imaging analysis showed that pregabalin was distributed up to the dermis in the PLO gel 1 h after application, while the aqueous solution was distributed near the epidermis. A significant analgesic effect (p < .05) was observed 1.5 h after PLO gel application in the DN model mice, but the aqueous solution had no effect. This study indicated for the first time that pregabalin penetrated beyond the skin epidermis up to the dermis, from the PLO gel formulation, and that the application of this formulation exhibited an in vivo analgesic effect in the mouse model of DN.

A Review on organogel for skin aging

Skin aging is one of the prominent problems associated with skin as each part of body ages with the time, skin is the external organ where the sign and symptoms of aging are readily evident. However cosmetics as well as pharmaceutical approaches delayed skin aging. Gel are best fitted in all these essential criteria because of their excellent appearance, smoothness, desired consistency, fast drug release, ease of manufacturing and quality assessment and admirable stability. Recently gel formulation have been modified to yield an advance drug delivery system known as ―organogels‖. Gel define as a semi-solid preparation having an external solvent phase, apolar [organogel] or polar [hydrogel] immobilized within the space available of a three dimensional network structure. Lecithin is a natural surfactant isolated from eggs or soya bean, when it combined with water and non-polar solvent, it form gels. PLO gels have gained importance in recent years as transdermal drug delivery system. It is a thermodynamically stable, visco-elastic system, which is non-irritating, odorless and biodegradable. Pluronic F127 or poloxamer is a copolymer of polyoxyethylene and polyoxypropylene which forms a thermoreversible gel in concentrations between 15-30%w/v. Water plays the role of a structure-forming agent and stabilizes the process of gel formation as it solubilizes the pluronic and other hydrophilic drugs. PLO gel system facilitates the delivery of hydrophilic as well as lipophilic drugs owing to the presence of both oil and aqueous phases within the gel system.

Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid

In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in varying concentrations to study various parameters using in vitro diffusion study and in vivo studies. All formulations were found to be off-white, homogenous, and reluctant to be washed easily and have pH value within the range of 5.56–5.80 which is nonirritant. Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were found to be more stable and retard the drug release from the gel. The formulations of F2 and F3 were selected for kinetic studies and stability studies, as they found to have all physical parameters within acceptable limits, highest percent drug content and exhibited highest drug release in eight hours. The order of drug release from various formulations was found to be F2 > F3 > F10 > F4 > F1 > F9 > F8 > F5 > F7 > F6. The optimized formulation F2 was found to follow zero order rate kinetics showing controlled release of the drug from the formulations. In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a standard marketed preparation (Volini gel) was found satisfactory and significant.

Organogels in Drug Delivery: A Special Emphasis on Pluronic Lecithin Organogels

Organogels have emerged as an alternative carrier for small and macromolecules via transdermal, oral, rectal and ophthalmic routes. Pluronic lecithin organogels (PLO gels) are lecithin-based organogels widely used in compounding pharmacies as a vehicle for enhancing the transdermal permeability of many therapeutic drugs. However, the scientific and systematic evidence in support of how well PLO gels help in transdermal delivery is scanty. Recently, some clinical studies have reported nearly complete lack of bioavailability of certain topically administered drugs from PLO gels. The present review aims at summarizing gels and organogels, with a focus on the use of PLO gels in transdermal drug delivery. A special emphasis is placed on controversies looming over the use of PLO gels as a delivery platform for drugs via transdermal route. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Organogels in Drug Delivery: A Special Emphasis on Pluronic Lecithin Organogels.

Organogels have emerged as an alternative carrier for small and macromolecules via transdermal, oral, rectal and ophthalmic routes. Pluronic lecithin organogels (PLO gels) are lecithin-based organogels widely used in compounding pharmacies as a vehicle for enhancing the transdermal permeability of many therapeutic drugs. However, the scientific and systematic evidence in support of how well PLO gels help in transdermal delivery is scanty. Recently, some clinical studies have reported nearly complete lack of bioavailability of certain topically administered drugs from PLO gels. The present review aims at summarizing gels and organogels, with a focus on the use of PLO gels in transdermal drug delivery. A special emphasis is placed on controversies looming over the use of PLO gels as a delivery platform for drugs via transdermal route.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Evaluation of the percutaneous absorption of chlorpromazine from PLO gels across porcine ear and human abdominal skin

ABSTRACTObjective: The overall objective of this work is to determine the percutaneous absorption of chlorpromazine hydrochloride from pluronic lecithin organogels (PLO gels) and verify the suitability of topically applied chlorpromazine hydrochloride PLO gels for use in hospice patients for relieving symptoms such as vomiting and nausea during the end stages of life.Methods: PLO gels of chlorpromazine hydrochloride were prepared using isopropyl palmitate (IPP) or ricinoleic acid (RA) as oil phase. In vitro percutaneous absorption of chlorpromazine hydrochloride was assessed through porcine ear and human abdominal skin. Further, the theoretical steady state plasma concentration (Css) of chlorpromazine was calculated from the flux values.Results: The pH, viscosity, and stability of both PLO gels prepared with IPP and RA were comparable. The thixotropic property of RA PLO gel was found to be better than that of IPP PLO gel. The permeation of chlorpromazine hydrochloride was higher from RA PLO gel than from IPP PLO gel and pure drug solution. Theoretical Css of chlorpromazine from pure drug solution, IPP PLO gel and RA PLO gel were found to be 1.05, 1.20, and 1.50 ng/ml, respectively. PLO gels only marginally increased the flux and theoretical Css of chlorpromazine.Conclusion: From this study, it is clearly evident that PLO gels fail to achieve required systemic levels of chlorpromazine following topical application. Chlorpromazine PLO gel may not be effective in treating nausea and vomiting for hospice patients with swallowing difficulties.

Percutaneous absorption of methimazole: an in vitro study of the absorption pharmacokinetics for two different vehicles

The use of transdermal medications in cats has become popular in veterinary medicine due to the ease of administration compared to oral medication. However, the research to support systemic absorption of drugs applied to the pinna after transdermal administration in cats is limited. The aim of this study was to characterize the percutaneous absorption pharmacokinetics of methimazole in a lipophilic vehicle compared to methimazole in Pluronic(®) lecithin organogel (PLO) using a finite dose applied to feline ear skin in an in vitro Franz cell model. The two formulations of methimazole (10mg) were applied to the inner stratum corneum of six pairs of feline ears. The receptor medium was sampled up to 30h post-administration, and methimazole concentrations were measured using high-performance liquid chromatography (HPLC). Histological examination of all ears was undertaken as small differences in the thickness of ear skin may have contributed to inter-individual differences in methimazole absorption between six cats. Methimazole was absorbed more completely across the pinnal skin when administered in the lipophilic vehicle compared to administration in the PLO gel (P<0.001).

Anti-inflammatory effects of a novel ricinoleic acid poloxamer gel system for transdermal delivery

Our previous study showed that the use of ricinoleic acid as an oil phase resulted in the formation of a stable pluronic lecithin organogel (PLO gel) with better thixotropic properties and higher permeation of ketoprofen than the isopropyl palmitate PLO gel. This study aims to evaluate and compare the in vitro and in vivo anti-inflammatory effects of the ricinoleic acid PLO gel system with isopropyl palmitate PLO gel. Ketoprofen was used as a model drug. In vitro anti-inflammatory activity and cell viability tests were performed in human rheumatoid arthritis synovial fibroblast cell line using a blank ricinoleic acid PLO gel and compared to that of the isopropyl palmitate PLO gel. In vivo anti-inflammatory activity of ricinoleic acid PLO gel containing 10% ketoprofen was evaluated and compared with the isopropyl palmitate PLO gel in a carrageenan-induced rat paw edema model. The results from the in vitro study showed that the blank ricinoleic acid PLO gel possessed significantly higher anti-inflammatory activity than isopropyl palmitate PLO gel at 1mM concentration (p<0.05), while both the gel formulations had no significant cytotoxic activity. Further in vivo testing of the formulation showed that the ricinoleic acid PLO gel formulation was significantly more effective in reducing pain and edema when compared to the isopropyl palmitate PLO gel. In addition, the ricinoleic acid PLO gel formulation markedly inhibited the synthesis of prostaglandin E2. In conclusion, the efficacy of PLO gels used in pain management may be enhanced by using ricinoleic acid instead of isopropyl palmitate as an oil phase.

Preclinical evaluation of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery.

Our previous study has shown that pluronic lecithin organogel (PLO gel) made of ricinoleic acid has the potential for use as a transdermal eyelid delivery system. The present study deals with the evaluation of ocular tissue concentrations of dexamethasone in a rabbit model following topical application of the gel formulation onto the eyelids. The PLO gel formulation containing dexamethasone was applied to the outside of the eyelid skin. Rabbits were sacrificed at regular time intervals of 2, 4, 8, 12, 20 and 24h. Maxidex(®) eye drops were used as a control. Rabbits were sacrificed and dexamethasone concentrations were analyzed in anterior segment tissues such as the cornea, conjunctiva, aqueous humor, lens, and iris-ciliary body by liquid chromatography tandem mass spectrometry (LC-MS/MS). Rabbit eyes were also examined for ocular irritation and scored using the modified Draize scoring system. No significant irritation or redness was observed in the eyes as compared to the control rabbit eyes. PLO gel formulation resulted in constant dexamethasone concentrations in the anterior segment tissues for up to 24h, which was equivalent or higher than Maxidex(®) eye drops. The findings of this investigation indicate that the ricinoleic acid PLO gel formulation may be clinically effective as a new treatment modality for anterior segment diseases.

Development and characterization of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery

Objective: This study deals with the preparation and evaluation of a pluronic lecithin organogel (PLO gel) containing ricinoleic acid for the transdermal eyelid delivery of dexamethasone and tobramycin.Methods: Five different PLO gel formulations (F1, F2, F3, F4 and F5) containing tobramycin (0.3%) and dexamethasone (0.1%) were prepared and compared to a conventional PLO gel (light mineral oil PLO gel, F6) with respect to physical appearance and viscosity. The optimized ricinoleic acid PLO gel formulation (F2) was further characterized for pH, gelation temperature, morphology and drug content. Ex vivo permeability of dexamethasone and bactericidal activity of tobramycin from formulation F2 was tested, and values were compared to the marketed Tobradex® eye ointment.Results: No apparent changes in the physical appearance and consistency were observed when ricinoleic acid was used as the oil phase. The pH of the optimized ricinoleic acid PLO gel (formulation F2) was found to be 6.54 with a gelation temperature of 31 °C. The drug content of tobramycin and dexamethasone were found to be 102.8% and 100.14%, respectively. The penetration profile of dexamethasone from formulation F2 was found to be much higher than the marketed Tobradex® eye ointment. F2 showed a better antimicrobial activity and higher zones of inhibition when compared to the marketed Tobradex® eye ointment.Conclusion: The findings of this investigation indicate that the ricinoleic acid PLO gel has the potential for use as a transdermal eyelid delivery system.

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.

Transdermal Evaluation of Caffeine in Different Formulations and Excipients

Background: The stratum corneum (SC) forms a difficult physical barrier for drugs to pass through the skin. Several strategies were developed to overcome this barrier. Optimization of topical drug formulations by selected excipients may facilitate the penetration of drugs through the SC into the viable skin cells and ultimately into the systemic circulation. Methods: Here, both the influence of two formulations (a classic carbomer-based gel and a novel Pluronic® lecithin organo gel (PLO gel)) and selected excipients (ethanol, propylene glycol, diethylene glycol monoethyl ether, isopropyl myristate (IPM), and water) with or without the penetration enhancer miconazole nitrate on the transdermal penetration characteristics of caffeine were determined using an in vitro Franz diffusion cell setup. Results: Higher fluxes were observed for the carbomer-based gel compared to the PLO gel. Among the commonly used excipients, IPM showed the best penetration enhancing properties, while the presence of the penetration...

Evaluation of Methadone Absorption After Topical Administration to Hospice Patients

Context Increased use of methadone (MTD) applied topically as an extemporaneously compounded gel was documented on routine review of medication profiles of hospice patients. A literature search did not identify any published clinical studies assessing the systemic absorption or clinical efficacy of MTD administered topically to intact skin for systemic pain. Objectives To compare serum MTD levels achieved after topical and oral administration to hospice patients. Methods To assess the absorption of MTD administered topically, two steady-state serum levels were determined in 10 patients administered MTD topically (10–45 mg/day as powder dissolved in ethoxydiglycol added to the calculated volume of pluronic lecithin organogel [PLO]), five patients administered MTD orally (PO) (15–40 mg/day), and one subject administered placebo topically. Results MTD levels from the subject administered placebo were <10 ng/mL. Eighteen of 20 serum MTD concentrations from nine patients administered topical MTD were identical to those in the placebo control. Only one of 10 patients administered topical MTD achieved measurable serum MTD levels. This patient was on the highest topical dose administered (45 mg/day) and achieved a mean serum concentration of 25.8 ng/mL (18–35 ng/mL). All MTD serum concentrations from patients administered oral MTD exceeded the lower limit of the reference range (10 ng/mL). The range of concentrations in the oral group ranged from 62 to 393 ng/mL (mean = 150.9 ng/mL). Conclusion The topical application of an MTD-PLO gel in doses <45 mg/day did not result in trough MTD serum concentrations associated with analgesia. An observer placebo response may explain the perceived benefit of MTD applied topically as a PLO gel in doses <45 mg/day. The evaluation of systemic absorption of MTD-PLO gel in doses >45 mg/day is warranted.