Physicochemical and dissolution profile characterization of pellets containing different binders obtained by the extrusion-spheronization process

With the purpose of evaluating the behavior of different polymers employed as binders in small-diameter pellets for oral administration, we prepared formulations containing paracetamol and one of the following polymers: PVP, PEG 1500, hydroxypropylmethylcellulose and methylcellulose, and we evaluated their different binding properties. The pellets were obtained by the extrusion/spheronization process and were subsequently subjected to fluid bed drying. In order to assess drug delivery, the United States Pharmacopeia (USP) apparatus 3 (Bio-Dis) was employed, in conjunction with the method described by the same pharmacopeia for the dissolution of paracetamol tablets (apparatus 1). The pellets were also evaluated for granulometry, friability, true density and drug content. The results indicate that the different binders used are capable of affecting production in different ways, and some of the physicochemical characteristics of the pellets, as well as the dissolution test, revealed that the formulations acted like immediate-release products. The pellets obtained presented favorable release characteristics for orally disintegrating tablets. USP apparatus 3 seems to be more adequate for discriminating among formulations than the basket method.

Novel formulation strategies for the fabrication of lyophilised orally disintegrating tablets

Orally disintegrating Tablets (ODTs), also known as fast-disintegrating, fast-melt or fast-dissolving tablets, are a relatively novel dosage technology that involves the rapid disintegration or dissolution of the dosage form into a solution or suspension in the mouth without the need for water. The solution containing the active ingredients is swallowed, and the active ingredients are then absorbed through the gastrointestinal epithelium to reach the target and produce the desired effect. Formulation of ODTs was originally developed to address swallowing difficulties of conventional solid oral dosage forms (tablets and capsules) experienced by wide range of patient population, especially children and elderly. The current work investigates the formulation and development of ODTs prepared by freeze drying. Initial studies focused on formulation parameters that influence the manufacturing process and performance of lyophilised tablets based on excipients used in commercial products (gelatin and saccharides). The second phase of the work was followed up by comprehensive studies to address the essential need to create saccharide free ODTs using naturally accruing amino acids individually or in combinations. Furthermore, a factorial design study was carried out to investigate the feasibility of delivering multiparticulate systems of challenging drugs using a novel formulation that exploited the electrostatic associative interaction between gelatin and carrageenan. Finally, studies aimed to replace gelatin with ethically and morally accepted components to the end users were performed and the selected binder was used in factorial design studies to investigate and optimise ODT formulations that incorporated drugs with varies physicochemical properties. Our results show that formulation of elegant lyophilised ODTs with instant disintegration and adequate mechanical strength requires carful optimisation of gelatin concentration and bloom strength in addition to saccharide type and concentration. Successful formulation of saccharides free lyophilised ODTs requires amino acids that crystallise in the frozen state or display relatively high Tg', interact and integrate completely with the binder and, also, display short wetting time with the disintegrating medium. The use of an optimised mixture of gelatin, carrageenan and alanine was able to create viscous solutions to suspend multiparticulate systems and at the same time provide tablets with short disintegration times and adequate mechanical properties. On the other hand, gum arabic showed an outstanding potential for use as a binder in the formulation of lyophilised ODTs. Compared to gelatin formulations, the use of gum arabic simplified the formulation stages, shortened the freeze drying cycles and produced tablets with superior performance in terms of the disintegration time and mechanical strength. Furthermore, formulation of lyophilised ODTs based on gum arabic showed capability to deliver diverse range of drugs with advantages over commercial products.

Solid dispersions: formulation, characterisation, permeability and genomic evaluation

Poor water solubility is characterised by low dissolution rate and consequently reduced bioavailability. Formulation of solid dispersion of the drug has attracted considerable interest as a means of improving dissolution process of a range of poorly water soluble drugs. This current study investigates the formulation of solid dispersion for a range of poorly water soluble drugs with varying physicochemical properties including paracetamol, sulphamethoxazole, phenacetin, indomethacin, chloramphenicol, phenylbutazone and succinylsulphathiazole. Solid dispersions were prepared using various drugs to polymer ratios. PEG 8000 was selected as a carrier in the solid dispersions. The study revealed that inclusion of drug within the polymeric matrix, ratio of drug to polymer and physicochemical properties of the drug molecules enhance the dissolution rate. Characterisations of the solid dispersions were performed using DSC, FTIR and SEM. These studies revealed that all seven drugs were present in the amorphous form within the solid dispersions and there was a lack of interaction between the PEG 8000 and drug. Stability studies for solid dispersions showed that all seven drugs studied were unstable at accelerated conditions (40°C±2°C/75%RH±5%RH) whereas, they were found to be stable for 12 months at room conditions. Permeability of indomethacin, phenacetin, phenylbutazone and paracetamol were higher for solid dispersions as compared to drug alone across Caco-2 cell monolayers. From the cell uptake studies it was shown that PEG 8000 enhanced rhodamine123 uptake which suggested that PEG 8000 may increase the permeability of these drugs in solid dispersions. Gene expression profiles analyzing the expression changes in the ABC and solute carrier transporter during permeability studies.ABCA10, ABCB4, ABCC12, SLC12A6, MCT13, SLC22A12 and SLC6A6 gene expression were increased by indomethacin alone whereas solid dispersion of indomethacin resulted in a slight increase in expression. ABCC12 and SAMC gene expression was increased in case of paracetamol alone but slightly increased when exposed to solid dispersion of paracetamol.

Formulation and characterisation of cationic microparticles for the delivery of DNA vaccines

The aim of this research was to formulate a novel biodegradable, biocompatible cationic microparticle vector for the delivery of DNA vaccines. The work builds upon previous research by Singh et al which described the adsorption of DNA to the surface of poly (D,L-lactide-co-glycolide) (PLG) microparticles stabilised with the surfactant cetyltrimethyl ammonium bromide (CT AB). This work demonstrated the induction of antibody and cellular immune responses to HIV proteins encoded on plasmid DNA adsorbed to the particle surface in mice, guinea pigs and non-human primates (Singh et aI, 2000; O'Hagan et aI, 2001). However, the use of surfactants in microparticle formulations for human vaccination is undesirable due to long term safety issues. Therefore, the present research aim was to develop an adsorbed DNA vaccine with enhanced potency and increased safety compared to CTAB stabilised PLG microparticles (PLG/CTAB) by replacement of the surfactant CTAB with an alternative cationic agent. The cationic polymers chitosan and poly (N- vinylpyrrolidone/2-dimethylaminoethyl methacrylate), dimethyl sulfate quaternary (PVP-PDAEMA) were investigated as alternative stabilisers to CTAB. From a variety of initial formulations, the most promising vector(s) for DNA vaccination were selected based on physicochemical data (chapter 3) and in vitro DNA loading and release characteristics (chapter 4). The chosen formulation(s) were analysed in greater depth (chapters 3 and 4), and gene expression was assessed by in vitro cell transfection studies using 293T kidney epithelial and C2C12 myoblast non-phagocytic cell lines (chapter 5). The cytotoxicity of the microparticles and their constituents were also evaluated in vitro (chapter 5). Stability and suitability of the formulation(s) for commercial production were assessed by cryopreparation and lyophilisation studies (chapters 3 and 4). Gene expression levels in cells of the immune response were evaluated by microparticle transfection of the dendritic cell (DC) line 2.4 and primary bone marrow derived DCs (chapter 6). In vivo, mice were injected i.m. with the formulations deemed most promising on the basis of in vitro studies and humoral and cellular immune responses were evaluated (chapter 6).

Physicochemical characteristics of chlorofluorohydrocarbon based inhalation aerosols

The aim of this work was to gain a better understanding of the physiochemical factors which affect the formulation of suspension inhalation aerosols. This has been attempted by applying the principles of colloid science to aerosol formulation. Both a drug system and a model colloid system have been used. The adsorption of six nonionic and cationic surfactants onto Spherisorb has been investigated. The results were analysed by calculating the area occupied by one adsorbed molecule at the surface and by comparing these values for each surfactant. The amount of each surfactant adsorbed was correlated with the number of sites on that surfactant molecule which could interact with the surface. The stability of suspensions, produced by both the model colloid Spherisorb, and by the drug isoprenaline sulphate, after adsorption of the surfactants, has been assessed by measuring settling times and rising times. The most stable suspensions were found to be those which had the greatest amounts of long chain fatty acid surfactant adsorbed on their surface. A comparison was made between the effective stabilising properties of Span 85 and oleic acid on various drug suspensions. It was found that Span 85 gave the most stable suspensions. Inhalation aerosol suspensions of isoprenaline sulphate were manufactured using the same surfactants used in the adsorption and suspension stability studies and were analysed by measuring the particle size distributions of the suspension and the emitted doses. The results were found to correlate with the adsorption and suspension stability studies and it was concluded that a deflocculated suspension was preferable to a flocculated suspension in inhalation aerosols provided that the drug density was less than the propellant density. The application of this work to preformulation studies was also discussed.

Formulation of immunomodulatory agents

Reversed-phase high-performance liquid chromatography procedures were developed for the analysis of pyrimidine-based drugs bropirimine and its derivatives (2-N-acetyl- and 2-N-propanoyl-) and for pyrimethamine and its 2/4- substituted derivatives (2, N-propanoyl and 2,4-N, N-dipropanoyl-) and its 6- substituted (methyl-, ethyl-, propyl- and isopropyl- carboxylates) analogues. Stability studies indicated that these derivatives were not sufficiently labile to act as potential prodrugs. Solubility-pH profiles were constructed from which the dissociation constants were calculated. The physicochemical properties of these compounds were studied and attempts were made to increase the poor aqueous solubility of bropirimine (35μg/mL) by prodrug synthesis, solvate formation (acetic acid, N, N-dimethylformamide and N-methylformamide) and the use of co-solvents and additives. The first two methods proved to be fruitless whereas the latter method resulted in an intravenous formulation incorporating 32mg/mL of bropirimine. An in-vitro method for the detection of precipitation was developed and the results suggested that by using low injection rates (< 0.24mL/min) and high mobile phase flow rates (> 500mL/hr) precipitation could be minimised. Differential scanning calorimetry showed that bropirimine debrominates in the presence of a number of additives commonly used in formulation work but the temperature at which this occurred were usually > 200oC. In-vitro work gave encouraging results for the possibility of rectal delivery of bropirimine but in-vivo work on rabbits showed considerable variations in the resulting plasma levels and pharmacokinetic parameters.

Formulation and development of cationic liposomes as adjuvants for subunit protein vaccinese

Liposomes remain at the forefront of vaccine design due to their well documented abilities to act as delivery vehicles and adjuvants. Liposomes have been described to initiate an antigen depot-effect, thereby increasing antigen exposure to circulating antigen-presenting cells. More recently, in-depth reviews have focussed on inherent immunostimulatory abilities of various cationic lipids, the use of which is consequently of interest in the development of subunit protein vaccines which when delivered without an adjuvant are poorly immunogenic. The importance of liposomes for the mediation of an antigen depot-effect was examined by use of a dual-radiolabelling technique thereby allowing simultaneous detection of liposomal and antigenic components and analysis of their pharmacokinetic profile. In addition to investigating the biodistribution of these formulations, their physicochemical properties were analysed and the ability of the various liposome formulations to elicit humoral and cell-mediated immune responses was investigated. Our results show a requirement of cationic charge and medium/strong levels of antigen adsorption to the cationic liposome in order for both a liposome and antigen depot-effect to occur at the injection site. The choice of injection route had little effect on the pharmacokinetics or immunogenicity observed. In vitro, cationic liposomes were more cytotoxic than neutral liposomes due to significantly enhanced levels of cell uptake. With regards to the role of bilayer fluidity, liposomes expressing more rigid bilayers displayed increased retention at the injection site although this did not necessarily result in increased antigen retention. Furthermore, liposome bilayer rigidity did not necessarily correlate with improved immunogenicity. In similar findings, liposome size did not appear to control liposome or antigen retention at the injection site. However, a strong liposome size correlation between splenocyte proliferation and production of IL-10 was noted; specifically immunisation with large liposomes lead to increased levels of splenocyte proliferation coupled with decreased IL-10 production.

Formulation and the characterisation of cationic liposomal adjuvants for the delivery of a promising subunit tuberculosis vaccine

Cationic liposomes of dimethyldioctadecylammonium bromide (DDA) incorporating the glycolipid trehalose 6,6-dibehenate (TDB) forms a promising liposomal vaccine adjuvant. To be exploited as effective subunit vaccine delivery systems, the physicochemical characteristics of liposomes were studied in detail and correlated with their effectiveness in vivo, in an attempt to elucidate key aspects controlling their efficacy. This research took the previously optimised DDA-TDB system as a foundation for a range of formulations incorporating additional lipids of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), by incrementally replacing the cationic content within DDA-TDB or reducing the total DDA-TDB dose upon its substitution, to ascertain the role of DDA and the effect of DDA-TDB concentration in influencing the resultant immunological performance upon delivery of the novel subunit TB vaccine, Ag85B–ESAT-6-Rv2660c (H56 vaccine). With the aim of using the DPPC based systems for pulmonary vaccine delivery and the DSPC systems for application via the intramuscular route, initial work focused on physicochemical characterisation of the systems with incorporation of DPPC or DSPC displaying comparable physical stability, morphological structure and levels of antigen retention to that of DDA-TDB. Thermodynamic analysis was also conducted to detect main phase transition temperatures and subsequent in vitro cell culture studies demonstrated a favourable reduction in cytotoxicity, stimulation of phagocytic activity and macrophage activation in response to the proposed liposomal immunoadjuvants. Immunisation of mice with H56 vaccine via the proposed liposomal adjuvants showed that DDA was an important factor in mediating resultant immune responses, with partial replacement or substitution of DDA-TDB stimulating Th1 type cellular immunity characterised by elevated levels of IgG2b antibodies and IFN-? and IL-2 cytokines, essential for providing protective efficacy against TB. Upon increased DSPC content within the formulation, either by DDA replacement or reduction of DDA and TDB, responses were skewed towards Th2 type immunity with reduced IgG2b antibody levels and elevated IL-5 and IL-10 cytokine production, as resultant immunological responses were independent of liposomal zeta potential. The role of the cationic DDA lipid and the effect of DDA-TDB concentration were appreciated as the proposed liposomal formulations elicited antigen specific antibody and cellular immune responses, demonstrating the potential of cationic liposomes to be utilised as adjuvants for subunit vaccine delivery. Furthermore, the promising capability of the novel H56 vaccine candidate in eliciting protection against TB was apparent in a mouse model.

The influence of formulation and manufacturing process parameters on the characteristics of lyophilized orally disintegrating tablets

Gelatin is a principal excipient used as a binder in the formulation of lyophilized orally disintegrating tablets. The current study focuses on exploiting the physicochemical properties of gelatin by varying formulation parameters to determine their influence on orally disintegrating tablet (ODT) characteristics. Process parameters, namely pH and ionic strength of the formulations, and ball milling were investigated to observe their effects on excipient characteristics and tablet formation. The properties and characteristics of the formulations and tablets which were investigated included: glass transition temperature, wettability, porosity, mechanical properties, disintegration time, morphology of the internal structure of the freeze-dried tablets, and drug dissolution. The results from the pH study revealed that adjusting the pH of the formulation away from the isoelectric point of gelatin, resulted in an improvement in tablet disintegration time possibly due to increase in gelatin swelling resulting in greater tablet porosity. The results from the ionic strength study revealed that the inclusion of sodium chloride influenced tablet porosity, tablet morphology and the glass transition temperature of the formulations. Data from the milling study showed that milling the excipients influenced formulation characteristics, namely wettability and powder porosity. The study concludes that alterations of simple parameters such as pH and salt concentration have a significant influence on formulation of ODT. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Strategic development and physicochemical analysis of oral preparations for unstable drugs

Oral liquid formulations are ideal dosage forms for paediatric, geriatric and patient with dysphagia. Dysphagia is prominent among patients suffering from stroke, motor neurone disease, advanced Alzheimer’s and Parkinson’s disease. However oral liquid preparations are particularly difficult to formulate for hydrophobic and unstable drugs. Therefore current methods employed in solving this issue include the use of ‘specials’ or extemporaneous preparations. In order to challenge this, the government has encouraged research into the field of oral liquid formulations, with the EMEA and MHRA publishing list of drugs of interest. The current work investigates strategic formulation development and characterisation of select API’s (captopril, gliclazide, melatonin, L-arginine and lansoprazole), each with unique obstacles to overcome during solubilisation, stabilisation and when developing a palatable dosage from. By preparing a validated calibration protocol for each of the drug candidates, the oral liquid formulations were assessed for stability, according to the ICH guidelines along with thorough physiochemical characterisation. The results showed that pH and polarity of the solvent had the greatest influence on the extent of drug solubilisation, with inclusion of antioxidants and molecular steric hindrance influencing the extent of drug stability. Captopril, a hydrophilic ACE inhibitor (160 mg.mL-1), undergoes dimerisation with another captopril molecule. It was found that with the addition of EDTA and HP-β-CD, the drug molecule was stabilised and prevented from initiating a thiol induced first order free radical oxidation. The cyclodextrin provided further steric hindrance (1:1 molar ratio) resulting in complete reduction of the intensity of sulphur like smell associated with captopril. Palatability is a crucial factor in patient compliance, particularly when developing a dosage form targeted towards paediatrics. L-arginine is extremely bitter in solution (148.7 g.L-1). The addition of tartaric acid into the 100 mg.mL-1 formulation was sufficient to mask the bitterness associated with its guanidium ions. The hydrophobicity of gliclazide (55 mg.L-1) was strategically challenged using a binary system of a co-solvent and surfactant to reduce the polarity of the medium and ultimately increase the solubility of the drug. A second simpler method was developed using pH modification with L-arginine. Melatonin has two major obstacles in formulation: solubility (100 μg.mL-1) and photosensitivity, which were both overcome by lowering the dielectric constant of the medium and by reversibly binding the drug within the cyclodextrin cup (1:1 ratio). The cyclodextrin acts by preventing UV rays from reaching the drug molecule and initiated the degradation pathway. Lansoprazole is an acid labile drug that could only be delivered orally via a delivery vehicle. In oral liquid preparations this involved nanoparticulate vesicles. The extent of drug loading was found to be influenced by the type of polymer, concentration of polymer, and the molecular weight. All of the formulations achieved relatively long shelf-lives with good preservative efficacy.

Physicochemical characterization of grewia polysaccharide gum:effect of drying method

Grewia polysaccharide gum, a potential pharmaceutical excipient was extracted from the inner stem bark of Grewia mollis, thereupon drying was achieved by three techniques: air-drying, freeze-drying and spray-drying. Analysis of the monosaccharide composition including 1H and 13C NMR spectroscopic analysis of the polysaccharide gum was carried out. The effect of the drying methods on the physicochemical properties of the gum was evaluated by Fourier transformed infra-red (FT-IR) spectroscopy, solid-state 13C nuclear magnetic resonance (NMR) spectroscopy, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis, differential scanning calorimetry and gel permeation chromatography. Monosaccharide sugar analysis revealed that the gum is composed of glucose, rhamnose, galactose, arabinose and xylose as the main neutral sugars. These were supported by the results from 1H and 13C NMR spectroscopic analysis. FT-IR and solid-state NMR results indicated that drying technique has little effect on the structure of the polysaccharide gum but XPS showed that surface chemistry of the gum varied with drying methods. Thermogravimetric analyses showed that oxidation onset varied according to the drying method. The molecular weight was also dependent on the drying technique. For industrial extrapolation, air-drying may be preferable to spray-drying and freeze-drying when relative cost, product stability and powder flow are required, for example in tablet formulation. © 2010 Elsevier Ltd. All rights reserved.

The effects of formulation and processing on surface characteristics and functional properties of dairy powders

The objectives of this thesis were to (i) study the effect of increasing protein concentration in milk protein concentrate (MPC) powders on surface composition and sorption properties; (ii) examine the effect of increasing protein content on the rehydration properties of MPC; (iii) study the physicochemical properties of spraydried emulsion-containing powders having different water and oil contents; (iv) analyse the effect of protein type on water sorption and diffusivity properties in a protein/lactose dispersion, and; (v) characterise lactose crystallisation and emulsion stability of model infant formula containing intact or hydrolysed whey proteins. Surface composition of MPC powders (protein contents 35 - 86 g / 100 g) indicated that fat and protein were preferentially located on the surface of powders. Low protein powder (35 g / 100 g) exhibited lactose crystallisation, whereas powders with higher protein contents did not, due to their high protein: lactose ratio. Insolubility was evident in high protein MPCs and was primarily related to insolubility of the casein fraction. High temperature (50 °C) was required for dissolution of high protein MPCs (protein content > 60 g / 100 g). The effect of different oil types and spray-drying outlet temperature on the physicochemical properties of the resultant fat-filled powders was investigated and showed that increasing outlet temperature reduced water content, water activity and tapped bulk density, irrespective of oil type, and increased solvent-extractable free fat for all oil types and onset of glass transition (Tg) and crystallisation (Tcr) temperature. Powder dispersions of protein/lactose (0.21:1), containing either intact or hydrolysed whey protein (12 % degree of hydrolysis; DH), were spray-dried at pilot scale. Moisture sorption analysis at 25 °C showed that dispersions containing intact whey protein exhibited lactose crystallisation at a lower relative humidity (RH). Dispersions containing hydrolysed whey protein had significantly higher (P < 0.05) water diffusivity. Finally, a spray-dried model infant formula was produced containing hydrolysed or intact whey as the protein with sunflower oil as the fat source. Reconstituted, hydrolysed formula had a significantly (P < 0.05) higher fat globule size and lower emulsion stability than intact formula. Lactose crystallisation in powders occurred at higher RH for hydrolysed formula. In conclusion, this research has shown the effect of altering the protein type, protein composition, and oil type on the surface composition and physical properties of different dairy powders, and how these variations greatly affect their rehydration characteristics and storage stability.

Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Feasibility Studies and Physicochemical Characterisation

Engineered cocrystals offer an alternative solid drug form with tailored physicochemical properties. Interestingly, although cocrystals provide many new possibilities, they also present new challenges, particularly in regard to their design and large-scale manufacture. Current literature has primarily focused on the preparation and characterization of novel cocrystals typically containing only the drug and coformer, leaving the subsequent formulation less explored. In this paper we propose, for the first time, the use of hot melt extrusion for the mechanochemical synthesis of pharmaceutical cocrystals in the presence of a meltable binder. In this approach, we examine excipients that are amenable to hot melt extrusion, forming a suspension of cocrystal particulates embedded in a pharmaceutical matrix. Using ibuprofen and isonicotinamide as a model cocrystal reagent pair, formulations extruded with a small molecular matrix carrier (xylitol) were examined to be intimate mixtures wherein the newly formed cocrystal particulates were physically suspended in a matrix. With respect to formulations extruded using polymeric carriers (Soluplus and Eudragit EPO, respectively), however, there was no evidence within PXRD patterns of either crystalline ibuprofen or the cocrystal. Importantly, it was established in this study that an appropriate carrier for a cocrystal reagent pair during HME processing should satisfy certain criteria including limited interaction with parent reagents and cocrystal product, processing temperature sufficiently lower than the onset of cocrystal Tm, low melt viscosity, and rapid solidification upon cooling.

A study of fish ice cream formulation by use of silver carp proteins instead of milk proteins

Fish is a valuable nutritional source witch use of it in daily meal has a beneficial role on nutritional needs supply and also causes mental and physical health especially in people who have protein and food deficiencies. Unfortunately, per capita consumption of sea foods in Iran is 5.5Kg witch is very lower than world standards. So, study on fish ice cream formulation, by use of fish protein concentrate (FPC) instead of milk protein, had done to make variation in sea foods products and also increase per capita consumption of these kinds of foods. FPC has very high protein concentration and a lot of necessary Also it's protein is very digestible amino acids like lysine and methionine with highly biological value and it's PER in compare with casein PER is high. At first fish protein concentrate type A produced from silver carp in three steps by the extraction with isopropyl alcohol solvent and heat. Microbiological and physicochemical specifications of produced FPC by rules of FDA and FAO were accepted. Finally according to panel test results, substitution of 30 percent of milk with FPC is acceptable. Also microbiological and physicochemical specifications of product were tested and results in compare with national standards of Iran were accepted.

Stability and Local Toxicity Evaluation of a Liposomal Prilocaine Formulation

This study reports a physicochemical stability evaluation of a previously reported liposomal prilocaine (PLC(LUV)) formulation (Cereda el al. J. Pharm. Pharmaceut. Sci. 7:235, 2004) before and after steam sterilization as well as its local toxicity evaluation. Prilocaine (PLC) was encapsulated into extruded unilamellar liposomes (LUVs) composed by egg phosphatidylcholine:cholesterol:alfa-tocopherol (4:3:0.07, mole %). Laser light-scattering analysis (p > 0.05) and thiobarbituric acid reaction (p > 0.05) were used to evaluate the liposomes physical (size) and chemical (oxidation) stability, respectively. The prilocaine chemical stability was followed by (1)H-nuclear magnetic resonance. These tests detected no differences on the physicochemical stability of PLC or PLCLUV, sterilized or not, up to 30 days after preparation (p > 0.05). Finally, the paw edema test and histological analysis of rat oral mucosa were used to assess the possible inflammatory effects of PLC(LUV). PLC(LUV) did not evoke rat paw edema (p > 0.05), and no significant differences were found in histological analysis, when compared to the control groups (p > 0.05). The present work shows that PLC(LUV) is stable for a 30-day period and did not induce significant inflammatory effects both in the paw edema test and in histological analysis, giving supporting evidence for its safely and possible clinical use in dentistry.