Aqueous Gel Formulation Research Articles

Semi-solid extrusion 3D printing of functionalized polyethylene oxide gels loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and valine-modified motherwort (Leonurus cardiaca L.) dry extract

Anxiety disorders are the most prevalent psychiatric disorders and are associated with a high burden of illness. Combining synthetic and native-origin compounds in treating such disorders could provide true benefits in terms of therapeutic efficacy. In the present study, we combined triazolobenzodiazepine and motherwort (Leonurus cardiaca L.) dry extract for such applications.
 The aim. The aim of this study was to develop aqueous polyethylene oxide (PEO) composite gels loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and a valine-modified motherwort herb dry extract for semi-solid extrusion (SSE) 3D printing. The printability of such gels and the physicochemical properties of the final 3D-printed drug preparations were investigated.
 Materials and methods. A new drug substance, 1,2,3-triazolo-1,4-benzodiazepine (MA-253) was synthesized and used to formulate oleogels and electrospun nanofibers for 3D printing. The plant-origin dry extract was prepared from a motherwort tincture and valine. The aqueous PEO gels loaded with a synthetic drug (MA-253) containing nanofibers and a valine-modified motherwort extract were prepared and subsequently used in the SSE 3D printing experiments. The homogeneity, viscosity and 3D printability of composite PEO gels were verified. The phytochemical assay of flavonoids in the 3D-printed drug preparations was conducted with the European pharmacopoeia spectrophotometric method.
 Research results. Three experimental gel formulations loaded with 1,2,3-triazolo-1,4-benzodiazepine nanofibers and a valine-modified motherwort dry extract were developed and tested for the SSE 3D printing applications. The present three gels showed good SSE 3D printability without any significant printing flaws. The SSE 3D-printed lattices prepared from the aqueous PEO gels containing 100 mg/ml of motherwort extract showed the most promising 3D printing performance. The 3D-printed drug preparations were entirely dissolved in purified water (22±2 °C) within 20 minutes, thus suggesting their applicability in oral administration.
 Conclusions. Novel aqueous PEO gel formulations loaded with nanofibrous 1,2,3-triazolo-1,4-benzodiazepine nanofibers and valine-modified motherwort herb extract are feasible for pharmaceutical SSE 3D printing. The present composite PEO gels enable the preparation of printed oral immediate-release drug delivery systems for new triazolobenzodiazepine derivatives and a drug therapy supportive plant extract

Semi-solid extrusion 3D-printing of eucalypt extract-loaded polyethylene oxide gels intended for pharmaceutical applications

In pharmaceutics, 3D printing is considered as a promising future technology for fabricating more complex patient-specific drug delivery systems (DDSs). An anti-staphylococcal herbal preparation, “Chlorophyllipt”, is produced mainly in a liquid form by the pharmaceutical industry in Ukraine, and it is composed of an ethanolic eucalypt extract (EE). Since staphylococcal infections have become a true challenge for the health care in all over the world, it would be relevant and justified to develop the aqueous gels of the present EE applicable for the 3D printing of the corresponding solid DDSs. The aim of the present study was to develop a novel polyethylene oxide (PEO) gel loaded with EE for a semi-solid extrusion (SSE) 3D printing and to print the corresponding oral solid DDSs with different sizes and shapes. For SSE 3D printing, we prepared and tested total ten (10) different aqueous PEO gel formulations loaded with EE. Prior to 3D printing, the physical appearance, homogeneity, injection force and viscosity of the gels were investigated. The EE-PEO gels were printed to lattice- and round-shaped solid DDSs with the head speed of 0.5 mm/s, and the weight (mass uniformity) and effective surface area of the printed systems were determined. The most feasible EE-PEO gel for SSE 3D printing comprised of 10 mg/ml of EE, 30 mg/ml of eumulgin and 20 mg/ml of ascorbic acid in a 20-% aqueous PEO gel. The key process parameters of the SSE 3D printing were identified and verified. The printing quality of EE-PEO DDSs were very good, thus showing compatibility of a plant extract and carrier polymer. Such 3D-printed antimicrobial DDSs can be used for example in the treatment of skin wounds and infections of the oral cavity.

Ionic liquids as tools to improve gel formulations containing sparingly soluble phenolic acids

Hydroxycinnamic acids, namely caffeic and p-coumaric acids, have several pharmaceutical and cosmetic applications, but due to their low aqueous solubility, their applicability can be limited. Ionic liquids (ILs) have been shown to be a valuable tool to improve the solubility and assist in the incorporation of various phenolic compounds into delivery systems. Thus, this work aims to evaluate the impact of incorporating three choline-based ILs, namely (2-hydroxyethyl)-trimethylammonium-L-phenylalanine [Cho][Phe], (2-hydroxyethyl)-trimethylammonium-L-glutamate [Cho][Glu] and (2-hydroxyethyl)-trimethylammonium-glycinate [Cho][Gly], into an aqueous gel formulation containing the poorly soluble caffeic and p-coumaric acids. The results obtained confirm that the ILs not only increase the drug solubility, but also allow higher amounts of both studied drugs to be incorporated into the gels, without interfering with the stability of the aqueous gels. Moreover, the ILs altered the fluidity of the gels, both in the absence and presence of both phenolic acids, as they increase the viscosity of the formulations, contributing to higher flow resistance of the gel, which may be better accepted by the consumer. Keywords: Ionic liquids; Hydroxycinnamic acids; Poorly soluble drugs; Gels; Increased Viscosity

Transdermal Delivery of a Hydrogen Sulphide Donor, ADT-OH Using Aqueous Gel Formulations for the Treatment of Impaired Vascular Function: an Ex Vivo Study

PurposeHydrogen sulphide (H2S) is an important signalling molecule involved in the regulation of several physiological and pathophysiological processes. The objective of this study was to investigate the feasibility of transdermal delivery of ADT-OH, a H2S donor, by investigating the transdermal flux of aqueous gels loaded with penetration enhancers or liposomes. Furthermore, we explored the ability of permeated ADT-OH to promote angiogenesis and mitochondrial bioenergetics in HUVEC cells.MethodsAqueous hypromellose gels (5% w/v) were prepared with up to 10% v/v propylene glycol (PG) or deformable liposomes with 0.025% w/w ADT-OH. ADT-OH permeation from formulations across excised murine skin into PBS was quantified over 24 h using HPLC-UV detection. Media was collected and applied to HUVEC cells to evidence ADT-OH functionality following permeation. Tube formation assays were performed as indicative of angiogenesis and mitochondrial oxygen consumption was evaluated using a Seahorse XF24.ResultsIncreasing the loading of PG caused an increase in ADT-OH permeation rate across skin and a decrease in dermal drug retention whereas liposomal gels produced a slow-release profile. Treatment of HUVEC’s using conditioned media collected from the ADT-OH loaded permeation studies enhanced tube formation and the basal oxygen consumption rates after 30 min of treatment.ConclusionsThese findings demonstrate that transdermal delivery of ADT-OH may provide a promising approach in the treatment of impaired vascular function. Gels prepared with 10% v/v PG have the potential for use in conditions requiring rapid H2S release whereas liposomal loaded gels for treatment requiring sustained H2S release.

Application of Plant Extracts as a Preservative in an Aqueous Gel Formulation

This research aims to study the antimicrobial activities of five selected plants, which were cinnamon bark, betel leaves, licorice, ginger, and galangal and select the most effective herbal extracts to be evaluated for their preservative efficacies in aqueous gel formulation. The sequential solvent extraction using hexane and 95% ethanol was used to extract bioactive constituents in the studied plants. After completely evaporated the solvents, the crude extracts were tested for the antimicrobial activities against S.aureus TISTR 1466 (ATCC 6538), P.aeruginosa TISTR 781 (ATCC 9027), E.coli ATCC 7839, C.albicans TISTR 5779 (ATCC 10201) and A.brasiliensis DMST 15538 (ATCC 16404) by agar well diffusion method. The result showed that the cinnamon bark extract macerated in hexane could inhibit the growth of all studied micro-organisms and was more effective than betel leaves, ginger, galangal and licorice extracts, while its 95% ethanolic extracts obviously showed lower antimicrobial activities. The MIC and MBC or MFC of cinnamon bark extract against the testing micro-organisms were in a range of 0.039-0.312 mg/mL and 0.156-1.250 mg/mL/0.078-0.625 mg/mL, respectively. The effective doses of hexane extract of cinnamon bark attempted to be tested as preservative in aqueous gel formulation were 0.3%, 1.25% and 2.5% by weight, which were equal to MIC, 4MIC and 8MIC, respectively. The challenge tests according to ISO 11930 were carried out to determine the preservative efficacy. The results revealed that 1.25% and 2.5% of cinnamon bark extract satisfied the criteria B for bacterial strains and the criteria A for yeast and mold. The LC-MS data confirmed that the two main constituents in hexane extract of cinnamon bark were coumarin and cinnamaldehyde that might play a role in antimicrobial activity.

Anti-HIV-1 activity and safety profile of a polyherbal gel formulation as a candidate microbicide

Microbicides represent one of the promising options for the prevention of sexually transmitted HIV infection. Medicinal plants have a long history of use to provide treatment against many diseases. In this regard, polyherbal aqueous gel formulation comprising 50% ethanolic extract prepared from the heart wood of Acacia catechu, leaves of Lagerstroemia speciosa, fruits of Aegle marmelos, Phyllanthus emblica and Terminalia chebula using carbopol 974 P NF polymer has been prepared. The gel formulation showed significant anti-HIV-1 activity against both CXCR4 tropic (HIV-1NL4.3) and CCR5 tropic (HIV-1NLAD8) viruses with IC50 values of 58.17 ± 4.4 and 63.54 ± 6.8 μg/ml respectively. It also showed significant inhibition of HIV-1 reverse transcriptase (p = 0.004), protease (p = 0.014), and integrase (p = 0.018) enzymes activity as compared to gel base. The gel formulation did not show any adverse effect on the viability of the vaginal lactobacilli, human vaginal keratinocytes (Vk2/E6E7), and the monolayer formed by Caco-2 cells. Furthermore, no significant changes in the secretion of pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF from the gel formulation treated Vk2/E6E7 cells were observed as compared to cells treated with gal base or medium control. Gel formulation did not show any significant increase in mutagenic index using Salmonella typhimurium. Gel formulation stored at either 30 ± 2 °C or 40 ± 2 °C was stable for 6 months for anti-HIV-1 activity. In conclusion, the polyherbal gel formulation reported herein having potent anti-HIV-1 activity and with limited safety profile may be a promising candidate as an herbal microbicide.

Pharmacokinetics of the Protein Microbicide 5P12-RANTES in Sheep following Single-Dose Vaginal Gel Administration.

5P12-RANTES, a chemokine analogue that potently blocks the HIV CCR5 coreceptor, is being developed as both a vaginal and rectal microbicide for prevention of sexual transmission of HIV. Here, we report the first pharmacokinetic data for 5P12-RANTES following single-dose vaginal gel administration in sheep. Aqueous gel formulations containing low (1.24-mg/ml), intermediate (6.18-mg/ml), and high (32.0-mg/ml; suspension-type gel) concentrations of 5P12-RANTES were assessed via rheology, syringeability, and in vitro release testing. Following vaginal gel administration to sheep, 5P12-RANTES concentrations were measured in vaginal fluid, vaginal tissue, and serum over a 96-h period. All gels showed non-Newtonian pseudoplastic behavior, with the high-concentration gels exhibiting a greater viscosity and cohesive structure than the intermediate- and low-concentration gels. In in vitro release testing, >90% 5P12-RANTES was released from the low- and intermediate-concentration gels after 72 h. For the high-concentration gel, ∼50% 5P12-RANTES was detected, attributed to protein denaturation during lyophilization and/or subsequent solvation of the protein within the gel matrix. In sheep, 5P12-RANTES concentrations in vaginal fluid, vaginal tissue, and serum increased in a dose-dependent manner. The highest concentrations were measured in vaginal fluid (105 to 107 ng/ml), followed by vaginal tissue (104 to 106 ng/ml). Both of these concentration ranges are several orders of magnitude above the reported half-maximal inhibitory concentrations. The lowest concentration was measured in serum (<102 ng/ml). The 5P12-RANTES pharmacokinetic data are similar to those reported previously for other candidate microbicides. These data, coupled with 5P12-RANTES's potency at picomolar concentrations, its strong barrier to resistance, and the full protection that it was observed to provide in a rhesus macaque vaginal challenge model, support the continued development of 5P12-RANTES as a microbicide.

Lanreotide autogel(®): a review of its use in the treatment of patients with acromegaly.

Lanreotide Autogel(®) (ATG) [Somatuline(®) Autogel(®), Somatuline(®) Depot(®)] is a prolonged-release, supersaturated aqueous gel formulation of the somatostatin analogue lanreotide acetate that acts via somatostatin receptors to reduce both growth hormone and insulin-like growth factor-I levels. It is indicated for the treatment of patients with acromegaly who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy. This article reviews the clinical efficacy and tolerability of lanreotide ATG in the treatment of acromegaly, as well as summarizing its pharmacological properties. Results of clinical trials and extension studies of up to 4years duration showed that deep subcutaneous lanreotide ATG was a generally effective treatment in treatment-naive and treatment-experienced adults with acromegaly. Lanreotide ATG provided hormonal control and improved both health-related quality of life and acromegaly symptoms in most patients; it also reduced tumour volume to a clinically significant extent in studies of primary therapy. Moreover, lanreotide ATG was generally no less effective than intramuscular lanreotide long-acting microparticles and was as effective as intramuscular octreotide long-acting release in switching or crossover studies, including those with standard or extended dosing intervals. Lanreotide ATG is generally well tolerated; the most frequently reported adverse events were mild or moderate transient gastrointestinal symptoms. Lanreotide ATG also has the advantage of being available in a convenient pre-filled syringe and is given subcutaneously rather than intramuscularly. Thus, lanreotide ATG continues to be a valuable option in the treatment of acromegaly, with potential advantages being ease of administration and longer dosing intervals in patients who have an adequate response to initial therapy.

Lanreotide in Metastatic Enteropancreatic Neuroendocrine Tumors

BackgroundSomatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited.MethodsWe conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor–positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety.ResultsMost patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant between-group differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group).ConclusionsLanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005–004904-35.)

Lanreotide extended-release aqueous-gel formulation, injected by patient, partner or healthcare provider in patients with acromegaly in the United States: 1-year data from the SODA registry

Lanreotide depot (LD; commercial name Somatuline® Depot) is an injectable, extended-release formulation of the synthetic somatostatin analog (SSA) lanreotide. In recent clinical trials, LD was found to be suitable for self or partner administration, avoiding the need to travel to a medical facility. The Somatuline® Depot for Acromegaly (SODA) study is an ongoing, multicenter, observational study in the US investigating the efficacy, safety, convenience and symptom relief provided by LD in patients with acromegaly. Sub-analyses explore outcomes according to who administered the injection: patient, partner, healthcare provider (HCP) or a combination. Data reported here reflect one year of patient experience. Patients are eligible for inclusion if they have a diagnosis of acromegaly, are treated with LD and can give signed informed consent. Baseline data include patient demographics, previous acromegaly treatment and investigations, GH and IGF-I levels, LD dose and dose adjustment frequency. Symptom frequency, injection pain and treatment convenience are assessed using patient-reported questionnaires. As of 18 April 2012, 166 patients had enrolled in SODA. Most (72 %) achieved normal IGF-I levels after 12 months of LD treatment. Disease control was similar in self or partner injectors and in patients who received injections from their HCP, although self or partner injecting was deemed more convenient. LD was well-tolerated irrespective of who performed the injection. Self injection led to more injection-site reactions, but this did not increase the rate of treatment interruption. Acromegaly symptoms remained stable. Biochemical, safety and convenience data support the clinical validity of injecting LD at home.

Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 μg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ~10(6)-fold greater than the 50% inhibitory concentrations (IC(50)s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle.

Early identification of availability issues for poorly water-soluble microbicide candidates in biorelevant media: A case study with saquinavir

In the search for a successful HIV microbicide, many poorly water-soluble antiviral agents are currently being investigated. Unfortunately, solubility and precipitation issues may limit intravaginal concentrations and thus availability of these agents upon application of an aqueous gel formulation. In the present study, we evaluated the in vitro precipitation behavior of the HIV protease inhibitor saquinavir in vaginal and seminal fluid simulants (VFS and SFS). Despite its limited solubility, the mesylate salt of saquinavir enables formulation of sufficiently high concentrations (2.5 mM, i.e. ca. 10 5-fold in vitro IC 50 values) in a standard aqueous vehicle. While saquinavir stays in solution upon dilution with VFS, SFS induces precipitation of saquinavir, resulting in a 5-fold reduced availability and antiviral potency. Inclusion of the solubilizing excipients polyethylene glycol 1000 (12%) and hydroxypropyl-β-cyclodextrin (2.5%) was required to avoid saquinavir precipitation in SFS and to restore the antiviral potency of the formulation. This study illustrates the importance of identifying solubility and precipitation issues of microbicide candidates in biorelevant media and provides a simple in vitro procedure to implement this evaluation in early microbicide development.

Using pH Abnormalities in Diseased Skin to Trigger and Target Topical Therapy

The pH discrepancy between healthy and atopic dermatitis skin was identified as a site-specific trigger for delivering hydrocortisone from microcapsules. Using Eudragit L100, a pH-responsive polymer which dissolves at pH 6, hydrocortisone-loaded microparticles were produced by oil-in-oil microencapsulation or spray drying. Release and permeation of hydrocortisone from microparticles alone or in gels was assessed, and preliminary stability data was determined. Drug release from microparticles was pH-dependent, though the particles produced by spray drying also gave significant non-pH-dependent burst release, resulting from their porous nature or from drug enrichment on the surface of these particles. This pH-responsive release was maintained upon incorporation of the oil-in-oil microparticles into Carbopol- and HPMC-based gel formulations. In vitro studies showed 4- to 5-fold higher drug permeation through porcine skin from the gels at pH 7 compared to pH 5. Permeation studies showed that the oil-in-oil-generated particles deliver essentially no drug at normal (intact) skin pH (5.0-5.5) but that delivery can be triggered and targeted to atopic dermatitis skin where the pH is elevated. The incorporation of these microparticles into Carbopol- and HPMC-based aqueous gel formulations demonstrated good stability and pH-responsive permeation into porcine skin.

Effect of gel composition and phonophoresis on the transdermal delivery of ibuprofen: In vitro and in vivo evaluation

The objective of this study was to evaluate the effect of formulation composition and continuous ultrasound at 1.5 W/Cm2 intensity on the permeation of ibuprofen across polymeric and biological barriers. In vitro studies were performed using cellulose membrane and rabbit skin, whereas in vivo studies were performed on rabbits. Overall, higher transport data were obtained with the cellulose membrane. Nonetheless, with both barriers, transport was higher with the gel formulation than oleaginous or emulsion based preparations, which was also dependent on the viscosity of the gel and the concentration of the formulation additives. Transport increased with the increase in alcohol concentration and decreased with the addition of propylene glycol. Ultrasound had a significant effect on ibuprofen transport. For example, an 11-fold increase in drug permeation across cellulose membrane was observed after the application of ultrasound. Similar effect was observed in animal studies. Ibuprofen plasma concentration increased with the concentration of the drug in the gel, which significantly increased after the application of ultrasound. It was concluded that aqueous gel formulations act as ideal coupling agents for topical application of drugs. Nonetheless, in addition to ultrasound, the composition of the gel is expected to have a significant effect on the transdermal delivery of drugs.

Effectiveness of self- or partner-administration of an extended-release aqueous-gel formulation of lanreotide in lanreotide-naïve patients with acromegaly

Surgical resection is often not curative in patients with acromegaly and long-acting somatostatin analogues (lanreotide or octreotide) are often needed. This study assessed the efficacy and safety of self- or partner-administration of lanreotide in patients with acromegaly. This was a six-month, single-arm, open-label study conducted at 13 endocrinology clinics. Fifty-nine patients received deep subcutaneous lanreotide injections every 28 days. Twelve patients started on 120 mg lanreotide and forty-seven started on 90 mg lanreotide. At week 16, the dose was adjusted to 60, 90 or 120 mg based on insulin-like growth factor-1 (IGF-1) levels at week 12. Fifty-nine patients with acromegaly either switched from long-acting octreotide (switch; n = 33) or were somatostatin analogue treatment-naïve or not currently taking long-acting octreotide (“other”; n = 26). The key endpoints included the percentage of patients/partners able to self- or partner-inject lanreotide and those with normal IGF-1 or growth hormone (GH) levels at week 24/early termination. 100% of patients/partners correctly self- (n = 41) or partner-injected (n = 18) lanreotide by week 4. By week 24/early termination, IGF-1 levels were controlled in 93.7% of switch and 46.2% of “other” patients, while GH levels were controlled in 76.9% and 39.1% of patients, respectively. Both IGF-1 and GH were controlled in 73.1% of switch and 30.4% of “other” patients. Most switch patients (81%) reported they preferred lanreotide over long-acting octreotide for future use (P = 0.0001). Self- or partner-administration of lanreotide is generally well tolerated and associated with IGF-1 and GH control in many lanreotide-naïve patients with acromegaly.

PREPARATION, IN-VITRO RELEASE AND ANTIINFLAMMATORY ACTIVITY OF MELOXICAM IN DIFFERENT GEL FORMULATIONS

This study was designed to evaluate different polymers to theirsuitability for formulation as vehicles for topical delivery system.Meloxicam (MX) was incorporated into the gel vehicles in aconcentration of 1.0% w/w. It is a non-steroidal anti-inflammatorydrug (NSAID) of the enolic acid class of compounds.Polymers used in this study are methylcellulose (MC), tylose(Ty), polyvinyl alcohol (PVA), poloxamer 407 (polo), polyethylene glycol (PEG), carbopol 974P (Carb. and eudispert mv. (Eud). Theyare used in a suitable concentration for gel formation.In-vitro release characteristics of the drug from different gelswere carried out using dialysis membrane in phosphate buffer pH6.8. The release data were treated with various kinetic principles toassess the relevant parameters.The general rank order of MX release was MC > Ty > polo >PVA > other gel forms. The results also showed that, the release ofdrug from the prepared gels obeyed the diffusion model (Higuchi’sequation).The influence of some formulation and processing variables(initial drug concentration of 0.5, 1.0 and 2.0% w/w, poloxamer407 concentration of 20, 25, 30% w/v in the aqueous gelformulation) on the release patterns have been studied. The resultsrevealed an inverse correlation between the drug release rate andthe poloxamer 407 concentration and direct correlation betweenthe drug release rate and the initial drug concentration.The anti-inflammatory activity of the drug in different gelformulations was studied using carrageenan induced rat pawedema method. The results obtained show an excellent antiinflammatoryactivity on rat paw edema.

Efficacy of a slow‐release formulation of lanreotide (Autogel® 120 mg) in patients with acromegaly previously treated with octreotide long acting release (LAR): an open, multicentre longitudinal study

Lanreotide Autogel 120 mg (ATG120; Ipsen S.p.A, Milan, Italy) is a high-dose, sustained-release aqueous gel formulation, supplied in a prefilled syringe and given by deep subcutaneous injection. The aim of this study was to compare efficacy and tolerability of ATG120 given every 4-8 weeks with those of octreotide LAR (o-LAR) given every 4 weeks. DESIGN PATIENTS AND INTERVENTION: A phase III multicentre Italian open clinical study of 23 acromegalic patients (15 female, 8 male). All patients had received o-LAR for 6-18 months and, after 3 months wash out, ATG120 was given every 6 weeks for a total of four injections (Period 1). Then the interval between ATG120 injections was adjusted according to three different schemes: every 4, 6 or 8 weeks depending on GH levels (GH > 2.5 microg/l; 1 < GH <or= 2.5 microg/l; GH <or= 1 microg/l, respectively). ATG120 was given for a further two to three doses, with a final assessment (Period 2) at Week 34, 36 or 42. Hormonal (GH and IGF-I) and clinical efficacy and tolerability. ATG120 induced a significant GH decrease from 9.9 +/- 11.3 at baseline (Visit 1) to 3.5 +/- 5.7 at the end of Period 1 (P < 0.01) and to 3.8 +/- 5.7 microg/l at the final visit (P < 0.01). IGF-I also decreased from 544 +/- 312 at baseline (Visit 1) to 318 +/- 181 at Period 1 and to 356 +/- 187 microg/l at the final visit (both P < 0.05 vs. baseline). The frequency of ATG120 administrations was adjusted to every 4 weeks in 12 patients, every 6 weeks in 4 patients and every 8 weeks in 6 patients; 1 patient withdrew before the dose adjustment. Serum GH and IGF-I achieved at the end of Period 1 and Period 2 were similar to those reached with o-LAR. The number of patients who achieved GH < 2.5 microg/l was comparable between o-LAR (43%) and ATG120 at Period 1 (48%) and at Period 2 (62%). Normal IGF-I levels were recorded in 8 patients during o-LAR (35%), 11 during ATG Period 1 (48%) and 10 at the final visit (43%). Last, 4 patients showed a better response to ATG120 and 2 to o-LAR. Lanreotide Autogel 120 mg is an effective and well-tolerated therapy for acromegaly. In approximately half of patients ATG120 may be administered every 6-8 weeks, instead of every 4 weeks, without lost of efficacy.

April Iotaderma (#159)

Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgarisJournal of the American Academy of DermatologyVol. 56Issue 3PreviewA new aqueous gel formulation of dapsone has been developed that allows clinically-effective doses of dapsone to be administered topically with minimal systemic absorption. Full-Text PDF

Unique aqueous gel formulation results in reduced risk of tretinoin-induced irritation

Unique aqueous gel formulation results in reduced risk of tretinoin-induced irritation

Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris

A new aqueous gel formulation of dapsone has been developed that allows clinically-effective doses of dapsone to be administered topically with minimal systemic absorption. The goal of these studies was to evaluate the efficacy and safety of dapsone gel, 5% in the treatment of acne. Patients 12 years of age and older with acne vulgaris (N = 3010) participated in two identically-designed 12-week, randomized, double-blind studies of twice-daily monotherapy with dapsone gel, 5%, versus a vehicle gel. Dapsone gel-treated patients achieved superior results in terms of the investigator's global acne assessment (P < .001) and the mean percentage reduction in inflammatory, noninflammatory, and total lesion counts (all, P < .001) at week 12. Reductions in inflammatory lesion counts favoring dapsone gel over vehicle were apparent as early as 2 weeks and reached statistical significance by 4 weeks. No clinically significant changes in laboratory parameters, including hemoglobin, even among glucose-6-phosphate dehydrogenase-deficient patients, were observed. Adverse events were comparable between the treatment groups and rarely led to discontinuation. Adjunctive topical treatments and their impact on acne were not studied in this trial. Dapsone gel, 5% appears to be an effective, safe, and well-tolerated treatment for acne vulgaris, with a rapid onset of action.