Formulation and rheological evaluation of ethosome-loaded carbopol hydrogel for transdermal application

Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailored for transdermal application that exhibits (i) plastic flow with yield stress of approximately 50–80?Pa at low polymer concentration, (ii) relatively frequency independent elastic (G′) and viscous (G″) properties and (iii) thermal stability.

Methods: Carbopol (C71, C934, C941, C971 or C974) hydrogels were prepared by dispersing Carbopol in distilled water followed neutralization by sodium hydroxide. The effects of Carbopol grade, Carbopol concentration, ethosome addition and temperature on flow (yield stress and viscosity) and viscoelastic (G′ and G″) properties of Carbopol hydrogel were evaluated. Based on the aforementioned rheological properties evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol hydrogel along with diclofenac-loaded ethosomal formulation as control.

Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of 0.50 and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a frequency independent G′ and G″. Furthermore, the flow and viscoelastic properties were maintained at the 4, 25 and 32?°C. The results from in vitro skin permeation studies indicate that ethosome-loaded C974 hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal formulation.

Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles.     

Design and in vitro characterization of buccoadhesive tablets of timolol maleate

Objective: The purpose of this work was to develop and evaluate buccoadhesive tablets of timolol maleate (TM) due to its potential to circumvent the first-pass metabolism and to improve its bioavailability.

Methods: The tablets were prepared by direct compression using two release modifying polymers, Carbopol 974P (Cp-974p) and sodium alginate (SA). A 3² full factorial design was employed to study the effect of independent variables, Cp-974p and SA, in various proportions in percent w/w, which influences the in vitro drug release and bioadhesive strengths. Physicochemical properties of the drug were evaluated by ultraviolet, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (P-XRD). Tablets were evaluated for hardness, thickness, weight variation, drug content, surface pH, swelling index, bioadhesive force and in vitro drug release.

Results: The FTIR and DSC studies showed no evidence of interactions between drug, polymers and excipients. The P-XRD study revealed that crystallinity of TM remain unchanged in optimized formulation tablet. Formulation F9 achieves an in vitro drug release of 98.967%?±?0.28 at 8?h and a bioadhesive force of 0.088 N?±?0.01211.

Conclusion: We successfully developed buccal tablet formulations of TM and describe a non-Fickian-type anomalous transport as the release mechanism.     

Oral Sustained-Release Bioadhesive Tablet Formulation of Didanosine

The objective of this study was to formulate a hydrogel-forming bioadhesive drug delivery system for oral administration of didanosine (ddI). The aim of this tablet dosage form is to improve the oral absorption of ddI by delivering it in small doses over an extended period and localizing it in the intestine by bioadhesion. Compressed tablets of ddI using Polyox® WSRN-303, Carbopol® 974P-NF, and Methocel® K4M as the bioadhesive release rate-controlling polymers were prepared. The effect of polymer concentration on the release profile and in vitro bioadhesion of the matrix tablets was studied. Tablet formulations with Polyox WSRN-303 (10%) and Methocel K4M (30%) showed 93 and 90% drug release, respectively, after 12 h. The drug release was found to be linear when fitted in the Higuchi equation (square-root time equation), suggesting zero-order release. Carbopol 974-P-NF was found to inhibit the complete release of ddI because of drug-polymer interaction; hence, is not suitable for formulation of ddI. Drug diffusion and swelling of the polymer (anomalous Fickian release) was found dominant in ddI release. In general, in vitro bioadhesion increased with an increase in polymer concentration. Tablets containing a single polymer can be designed to form hydrogels serving the dual purpose of bioadhesion and sustained release.     

Oral sustained-release bioadhesive tablet formulation of didanosine

The objective of this study was to formulate a hydrogel-forming bioadhesive drug delivery system for oral administration of didanosine (ddI). The aim of this tablet dosage form is to improve the oral absorption of ddI by delivering it in small doses over an extended period and localizing it in the intestine by bioadhesion. Compressed tablets of ddI using Polyox® WSRN-303, Carbopol® 974P-NF, and Methocel® K4M as the bioadhesive release rate-controlling polymers were prepared. The effect of polymer concentration on the release profile and in vitro bioadhesion of the matrix tablets was studied. Tablet formulations with Polyox WSRN-303 (10%) and Methocel K4M (30%) showed 93 and 90% drug release, respectively, after 12 h. The drug release was found to be linear when fitted in the Higuchi equation (square-root time equation), suggesting zero-order release. Carbopol 974-P-NF was found to inhibit the complete release of ddI because of drug-polymer interaction; hence, is not suitable for formulation of ddI. Drug diffusion and swelling of the polymer (anomalous Fickian release) was found dominant in ddI release. In general, in vitro bioadhesion increased with an increase in polymer concentration. Tablets containing a single polymer can be designed to form hydrogels serving the dual purpose of bioadhesion and sustained release.     

Pharmaceutical and Medical Aspects of Bioadhesive Systems for Drug Administration

Abstract

Bioadhesion could lead to the solution of bioavailability problems resulting from a too short stay of the pharmaceutical dosage form at the absorption or activity level of the active ingredient. Bioadhesion stages are: intimate contact resulting from a good wetting of the bioadhesion surface and the swelling of the bioadhesive polymer, then penetration of the bioadhesive into the crevice of the tissue surface or interpenetration of bioadhesive chains with those of the mucus, and finally low chemical bonds. date, the most important bioadhesive polymers are polycarbophil a Carbopol 934. Methods of studying bioadhesion are described as well as the existing bioadhesive dosage forms.     

Formulation and characterization of a captopril ethyl ester drug-in-adhesive-type patch for percutaneous absorption

Background: The ethyl ester of captopril has been shown to exhibit enhanced permeation across human skin compared to the parent drug. A drug-in-adhesive patch formulation of a captopril ethyl ester was therefore developed for optimum drug release. Method: A wide range of transdermal patches were prepared using two commercially available bioadhesive polymers. Investigational screening was conducted on the patches using microscopy, texture profile analysis, and infrared spectroscopy. Drug release profiles of suitable patches were obtained using both polydimethylsiloxane (Silastic?) and porcine skin in vitro. Results: Diffusion results across Silastic? showed a gradual plateau in flux with increased drug loading that may be attributable to intramolecular interactions while flux across porcine skin was seen to increase with increasing patch thickness and attained a therapeutic level. Conclusions: This study demonstrated that adhesion and drug loading are significant factors in optimizing a topical patch formulation for the delivery of a captopril prodrug.     

Mucoadhesive Drug Delivery Systems

Abstract

Pharmaceutical aspects of mucoadhesion have been the subject of great interest during recent years because mucoadhesion could be a solution for bioavailability problems that result from a too short length of stay of the pharmaceutical dosage form at the absorption site within the gastro-intestinal tract.

This paper describes some aspects of bioadhesion such as mucus structure, stages of adhesion and the theories proposed that attempt to explain the adhesion mechanism. The factors that affect the bioadhesive power of a polymer, the methods that permit the evaluation of a bioadhesive system and the methods for surface characterization of biomaterials are discussed. Finally, the various polymers used and the bioadhesive systems designed for several therapeutic purposes are presented.     

Assemblies for In Vitro Measurement of Bioadhesive Strength and Retention Characteristics in Simulated Vaginal Environment

ABSTRACT

The vaginal route of administration offers a promising option for local and systemic delivery of drugs. Conventional vaginal formulations are associated with limitations of poor retention, leakage, and messiness, thereby causing inconvenience to users. To overcome these limitations, formulations that adhere to the vaginal mucosa for a sufficient period of time need to be developed. Bioadhesion and retention are desirable characteristics of a vaginal formulation to achieve desired efficacy. These properties can be built in during formulation development by the use of bioadhesive polymers. In the present study, assemblies for in vitro measurement of bioadhesive strength and retention characteristics of vaginal formulations have been developed. A modified simulated vaginal fluid (SVF_M) was used to simulate vaginal conditions for bioadhesion studies. Cellophane hydrated with SVF_M and isolated sheep vaginal mucosa were used as model membranes. The bioadhesive potential of various polymers and their combinations was evaluated. Among the polymers evaluated, xanthan gum (XG), sodium alginate (SA), Polycarbophil (PC), and their combinations (XG + SA and XG + PC) were found to possess significant bioadhesive strength. In retention experiments, XG, SA, and combinations (XG + SA and XG + PC) were retained in isolated sheep vaginal tissue, while PC exhibited poor retention under experimental conditions. Based on the results of the study conducted, XG, SA, and combinations (XG + SA and XG + PC) have been proposed as potential candidates for developing bioadhesive vaginal drug delivery systems.     

Development of topical hydrogels of terbinafine hydrochloride and evaluation of their antifungal activity

The purpose of this study was to prepare hydrogels and microemulsion (ME)-based gel formulations containing 1% terbinafine hydrochloride (TER-HCL) and to evaluate the use of these formulations for the antifungal treatment of fungal infections. Three different hydrogel formulations were prepared using chitosan, Carbopol® 974 and Natrosol® 250 polymers. A pseudo-ternary phase diagram was constructed, and starting from ME formulation, a ME gel form containing 1% Carbopol 974 was prepared. We also examined the characteristic properties of the prepared hyrogels. The physical stability of hydrogels and the ME -based gels were evaluated after storage at different temperatures for a period of 3 months. The release of TER-HCL from the gels and the commercial product (Lamisil®) was carried out by using a standard dialysis membrane in phosphate buffer (pH 5.2) at 32?°C. The results of the in vitro release study showed that the Natrosol gel released the highest amount of drug, followed by Carbopol gel, chitosan gel, commercial product, and the microoemulsion-based gel in that order. In vitro examination of antifungal activity revealed that all the prepared and commercial products were effective against Candida parapsilosis, Penicillium, Aspergillus niger and Microsporum. These results indicate that the Natrosol®-based hydrogel is a good candidate for the topical delivery of TER-HCL.     

Novel cyclodextrin-based film formulation intended for buccal delivery of atenolol

Background: Unknown influence of cyclodextrin on the properties of the film formulation aimed for buccal application. Aim: Development and characterization of a novel bioadhesive film formulation for buccal atenolol delivery containing drug/cyclodextrin inclusion. Method: Interaction between atenolol and randomly methylated β-cyclodextrin (RAMEB) in solution was studied by phase solubility studies. The complex in solid state was prepared by the freeze-drying method and characterized by differential scanning calorimetry and Fourier-transformed infrared spectroscopy (FTIR). The drug, free or in complex form, was incorporated into polymeric films prepared by the casting method using ethylcellulose (EC), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC). The prepared film formulations were characterized in terms of swelling, bioadhesion, and in vitro drug release. Results: The formation of a stabile inclusion complex (K_s = 783.4?±?21.6 M^?1) in 1:1 molar stoichiometry was confirmed in solution and in solid state. The swelling properties of films were predominated by the type of polymer used in the formulation. In vitro bioadhesive properties of the films were well correlated with the swelling properties of the polymers used in the formulation. Although incorporation of the drug, free or in complex form, decreased the bioadhesion of the films, PVA- and HPMC-based formulations retained suitable bioadhesive properties. Higher atenolol solubility upon complexation with RAMEB increased the drug dissolution rate under conditions designed to be similar to those on the buccal mucosa, but it has decreased the drug release rate from the PVA and HPMC film formulation, leading to a sustained drug release pattern. In the case of EC-based films, RAMEB promoted drug release. Other parameters that influenced the drug release rate were associated with the structure of the polymer used in the formulation, swelling characteristics of the films, and the interaction between atenolol and hydrophilic polymers that was demonstrated by FTIR analysis. Conclusion: Incorporation of atenolol in the form of an inclusion complex into hydrophilic films may be an appropriate strategy to prepare a suitable formulation for buccal drug delivery.     

Design,Development, and Biopharmaceutical Properties of Buccoadhesive Compacts of Pentazocine

Buccoadhesive compacts (BCs) of pentazocine (PZ) were prepared by the direct compression method using polymers like carbopol 974P (CP 974P) and hydroxypropyl methylcellulose (HPMC K4M) in ratios of 1:0 (batch B₁), 1:1 (B₂), 1:2 (B₃), 1:4 (B₄), and 0:1 (B₅). The compacts were evaluated for thickness uniformity, weight variation, drug content uniformity, and swelling index. Swelling was increased with an increase in HMPC K4M content in the compacts. An in vitro assembly was developed to measure and compare the bioadhesive strength of compacts. The maximum bioadhesive strength was observed in compacts formulated with a combination of CP 974P and HPMC K4M. The compacts were evaluated in vitro for 24 hr in pH 6.6 phosphate buffer using a standardized dissolution apparatus. The data were evaluated by a simple power equation (M_t/M_∞ = Ktⁿ); it was observed that all the compacts followed non-Fickian release kinetics. Some of the buccoadhesive compacts were evaluated in vivo in rabbits. The compacts gave controlled blood level profiles with a twofold to threefold increase in area-under-the-curve (AUC) values in comparison to oral administration of aqueous drug solution.     

Buccoadhesive Tablets of Nifedipine: Standardization of A Novel Buccoadhesive-Erodible Carrier

Abstract

Buccoadhesive tablets of nifedipine were obtained by incorporation of nifedipine in suitable carrier systems standardised based on bioadhesion and dissolution. The carrier systems were formulated using sodium alginate as the bioadhesive. Mannitol, lactose, polyethylene glycol 6000 and polyethylene glycol 4000 were incorporated as solubilisers, singly or in combination. Carrier systems having a diameter of 11 mm and weighing about 200 mg were obtained by standard tabletting techniques using polyvinylpyrolidone as the binder. The systems were evaluated for bioadhesion and dissolution, 'in vitro' and 'in vivo' in seven normal healthy human volunteers. Based on these studies, nifedipine (5 mg) was incorporated in selected carrier systems to obtain buccoadhesive tablets of nifedipine. These tablets exhibited rapid 'in vitro' drug release.     

Nanostructured lipid carriers based nanogel for meloxicam delivery: mechanistic,in-vivo and stability evaluation

Aim: Our investigation was aimed to investigate the potential suitability of meloxicam-loaded nanostructured lipid carriers (MLX-NLC) gel for topical application.

Main methods: MLX-NLC gel was prepared and in vivo skin penetration ability of the NLC gel was evaluated using confocal laser scanning microscopy. We studied the effect of MLX-NLC gel on the changes in lipid profile of skin to get an insight into its skin penetration enhancement mechanism. Acetic acid induced writhing test was performed to evaluate the analgesic effect. Drug concentration-time profile of MLX in rat plasma and skin after topical and oral treatment with MLX-NLC gel and oral MLX-solution, respectively, was observed. MLX-NLC gel was subjected to primary skin irritation test, sub-acute dermal toxicity study. Storage stability of MLX-NLC gel was also assessed for 90 days.

Key findings: NLC gel was effective in permeating Rhodamine 123 to deeper layers of rat skin. Changes in skin lipid prolife were observed in the rat skin on treatment with MLX-NLC gel and the results supported skin lipid extraction as a possible penetration enhancement mechanism. MLX-NLC gel demonstrated sustained pain inhibitory effect. Pharmacokinetics study established that topical application of MLX-NLC gel had the potential to avoid systemic uptake and hence the risk of systemic adverse effects. MLX-NLC gel demonstrated good skin tolerability and biosafety. Excellent physical stability of nanogel was observed at 4?±?2?°C.

Significance: The study revealed that NLC gel is a promising carrier system for the topical application of MLX without side effects.     

Mucoadhesive Drug Delivery Systems

Mucoadhesion in drug delivery systems has recently gained interest among pharmaceutical scientists as a means of promoting dosage form residence time as well as improving intimacy of contact with various absorptive membranes of the biological system. Besides acting as platforms for sustained-release dosage forms, bioadhesive polymers can themselves exert some control over the rate and amount of drug release, and thus contribute to the therapeutic advantage of such systems. This paper describes some aspects of bioadhesion such as mucus layer, mucoadhesion, and theories of bioadhesion to explain the adhesion mechanism. The factors important to mucoadhesion, the methods used to study bioadhesion, and bioadhesive polymers are described. The methods that evaluate the mucoadhesive dosage forms and finally the bioadhesive drug delivery systems designed for several therapeutic purposes are presented.     

Exploring the antioxidant potentiality of two food by-products into a topical cream: stability,in vitro and in vivo evaluation

Abstract

Context: Coffee silverskin (CS), a food by-product of the coffee roasting industry, has been studied as an active ingredient for skin care products due to its high potential of antioxidant activity and low cytotoxicity. Another food waste used as ingredient with promising characteristics is obtained from Medicago sativa (MS), which antioxidants and isoflavones content is high.

Objective: The aim of this study is to evaluate and characterize a new body formulation containing two food by-products extracts.

Materials and methods: Different parameters (such as pH, rheological behavior, color, antioxidant content and microbiological analysis) of a body cream formulation containing by-products (CSMS) and a formulation without extracts (F) were evaluated under a stability study during 180 days at different temperatures. Moreover, the in vitro cell toxicity and the in vivo skin safety and protective effects were also assessed.

Results: Formulation showed stable physical properties and antioxidant activity during 180 days of storage. In vitro toxicity was screened in two skin cell lines (fibroblasts and keratinocytes) and any toxicity was reported. The in vivo test carried out showed that, with respect to irritant effects, CSMS formulation can be regarded as safe for topical application and the skin hydratation improved after 30 days of its use. Also, considering the consumer acceptance, more than 90% of volunteers classified it as very pleasant.

Conclusions: CSMS formulation is stable and safe for topical use as no adverse and/or side effects were observed during the application period of testing, improving skin protective properties.     

Hydrogels containing rutin intended for cutaneous administration: efficacy in wound healing in rats

Objective: Development of a hydrogel containing rutin at 0.025% (w/w) and evaluation of its in vivo efficacy in cutaneous wound healing in rats.

Methods: Hydrogels were prepared using Carbopol Ultrez^® 10 NF and an aqueous dispersion of rutin in polysorbate 80. Hydrogels were characterized by means of pH measurement, rheological and spreadability analysis and rutin content determination by liquid chromatography. The in vivo healing effect was evaluated through the regression of skin lesions in rats and by analysis of oxidative stress.

Results and discussion: Hydrogels showed adequate pH values (5.50–6.50) and pseudoplastic non-Newtonian behavior. After 5 days of treatment of wounds, hydrogels containing rutin presented a higher decrease in the wound area compared to the control hydrogels. Analysis of the oxidative stress showed a decrease in lipid peroxidation and protein carbonyl content as well as an increase in catalase activity after the treatment with the hydrogel containing rutin. Furthermore, this treatment increased total protein levels.

Conclusion: This study shows for the first time the feasibility of using dermatological formulations containing rutin to improve skin wound healing.     

Production of Carbopol® 974P and Carbopol® 971P Pellets by Extrusion‐Spheronization: Optimization of the Processing Parameters and Water Content

Pellets obtained by extrusion‐spheronization represent multiparticulate dosage forms whose interest in intestinal drug delivery can be potentiated and targeted through bioadhesive properties. However, adhesion itself makes the process difficult or even impossible. The problem of tackiness encountered with bioadhesive wet masses was previously eliminated by the use of electrolytes such as CaCl₂. This approach is known to reduce the viscosity of polyacrylic acids by disturbing the interactions between carboxylate groups on adjacent polymer molecules, thereby decreasing their bioadhesive properties. The present study aimed at producing pellets containing carbomers without addition of electrolytes in order to maintain their bioadhesive potentiality at its maximum. Carbopol® 974P (10%, 15% and 20%) and Carbopol® 971P (10%) were used in combination with Avicel® PH101. The extrusion speed (30, 45, 60, 90, and 150 rpm), spheronizer speed (350, 700, 960, 1000, and 1300 rpm), spheronization time (5, 10, 15, and 20 minutes) and amount of water (45%, 50%, 54%, and 58%) were optimized in order to obtain the highest yield of spherical pellets ranging 710–1000 µm in diameter. For pellets containing 10%, 15% Carbopol® 974P or 10% Carbopol® 971P and 45% water content, 30 rpm extrusion speed, 960 rpm, and 10 minutes spheronization speed and time led to the highest yields and sphericities, respectively, 72% and 0.91, 67% and 0.78, and 76% and 0.80. Production of pellets with 20% Carbopol® 974P could be achieved through the increase of the water content up to 58% and implementation of 30 rpm extrusion speed, 1300 rpm, and 10 minutes spheronization speed and time. The yield and sphericity were 42% and 0.78 respectively.     

Optimization of Sotalol Floating and Bioadhesive Extended Release Tablet Formulations

Abstract

A novel extended release sotalol HC1 tablet formulation which possesses a unique combination of floatation and bioadhesion for prolonged residence in the stomach has been developed. Tablets were produced by direct compression. A two-factor factorial, central, composite Box-Wilson experimental design was employed to develop and optimize the tablet formulation containing 240 mg sotalol HC1. The ratio of two major bioadhesive agents, sodium carboxymethylcellulose (NaCMC) to hydroxypropylmethylcellulose (HPMC), and the ratio of two direct compressible diluents, ethylcellulose (EC) to crosspovidone, were used as formulation variables (independent variables) for optimizing tablets response parameters, such as dissolution bioadhesive capability, tablet density and required compression force for producing 6 Kg hardness tablets. The data were also analyzed by means of quadratic response surface model. Response surfaces were generated as a function of formulation variables. An optimum direct compression, bioadhesive and floating tablet formulation of sotalol HCl was achieved by considering the dissolution characteristic as primary objective and using required compression force, bioadhesive capability as constraints within the experimental region. The surface model was validated for accurate prediction of response characteristics.     

Development,optimization, and characterization of a novel tea tree oil nanogel using response surface methodology

Purpose: To develop and optimize nanoemulsion (NE)-based emulgel (EG) formulation as a potential vehicle for topical delivery of tea tree oil (TTO).

Methodology: Central composite design was adopted for optimizing the processing conditions for NE preparation by high energy emulsification method viz. surfactant concentration, co-surfactant concentration, and stirring speed. The optimized NE was developed into emulgel (EG) using pH sensitive polymer Carbopol 940 and triethanolamine as alkalizer. The prepared EG was evaluated for its pH, viscosity, and texture parameters, ex vivo permeation at 37?°C and stability. Antimicrobial evaluation of EG in comparison to conventional gel and pure TTO was also carried out against selected microbial strains.

Results and discussion: Optimized NE had particle size and zeta potential of 16.23?±?0.411?nm and 36.11?±?1.234?mV, respectively. TEM analysis revealed the spherical shape of droplets. The pH of EG (5.57?±?0.05?) was found to be in accordance with the range of human skin pH. EG also illustrated efficient permeation (79.58?μL/cm²) and flux value (J_SS) of 7.96?μL cm²/h through skin in 10?h. Viscosity and texture parameters, firmness (9.3?±?0.08?g), spreadability (2.26?±?0.06?mJ), extrudability (61.6?±?0.05?mJ), and adhesiveness (8.66?±?0.08?g) depict its suitability for topical application. Antimicrobial evaluation of EG with same amount of TTO as conventional gel revealed broader zones of growth inhibitions against all the selected microbial strains. Moreover, EG was also found to be nonirritant (PII 0.0833). These parameters were consistent over 90 d.

Conclusion: TTO EG turned out to be a promising vehicle for the topical delivery of TTO with enhanced therapeutic efficacy.     

Preparation and characterization of bioadhesive systems containing propolis or sildenafil for dental pulp protection

Purpose: Binary polymeric systems containing poloxamer 407 (P407) and Carbopol 934P (C934P) were designed to deliver propolis extract (PE) or sildenafil citrate for the endodontic treatment (pulp protection).

Methods: Gelation temperature, rheology (flow), bioadhesion, and in vitro drug release of formulations were determined.

Results: Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34–37°C. In addition, they exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. The greatest bioadhesion was noted in the formulation containing 20% P407 (w/w) and 0.10% C934P (w/w). PE release from formulation containing 15% P407 (w/w) and 0.25% C934P (w/w) was controlled by the phenomenon of relaxation of polymer chains. Moreover, sildenafil release from formulation containing 20% P407 (w/w) and 0.10% C934P (w/w) was controlled by Fickian diffusion.

Conclusion: The data obtained on these formulations indicate a potentially useful role in the endodontic treatment (pulp protection) and suggest they are worthy of clinical evaluation.