International Journal of Pharmaceutics (v.345, #1-2)

Reviews Editor for IJP by Alexander T. Florence; Howard Rytting; T. Sonobe (1).

Disintegration is a performance test for oral dosage forms that is described in the United States Pharmacopeia (USP), the European Pharmacopeia (EP) and the Japanese Pharmacopeia ().This review lists changes that have been made since the USP 23 and compares them to those in the USP 30, EP 5.3 and JP XIV. The differences between the disintegration test methods in the three pharmacopeias are discussed. Examples are provided where disintegration can be used as a performance test for ensuring the drug release.
Keywords: Disintegration; USP; Pharmacopeia; Performance test; Solid oral dosage forms; Liquid filled capsules; ICH;

Stable drug encapsulation in micelles and microemulsions by Ajit S. Narang; David Delmarre; Danchen Gao (9-25).
Oral absorption of hydrophobic drugs can be significantly improved using lipid-based non-particulate drug delivery systems, which avoid the dissolution step. Micellar and microemulsion systems, being the most dispersed of all, appear the most promising. While these systems show high drug entrapment and release under sink conditions, the improvement in oral drug bioavailability is often unpredictable. The formulation and drug-related biopharmaceutical aspects of these systems that govern oral absorption have been widely studied. Among these, preventing drug precipitation upon aqueous dilution could play a predominant role in many cases. Predictive ability and quick methods for assessment of such problems could be very useful to the formulators in selecting lead formulations. This review will attempt to summarize the research work that could be useful in developing these tools.
Keywords: Bioavailability; Hydrophobic drugs; Micelles; Microemulsions; Precipitation; SEDDS; SMEDDS; Self-emulsifying; Solubilization; Self-microemulsifying;

Nanostructures from alkyl vitamin C derivatives (ASC n ): Properties and potential platform for drug delivery by Santiago Palma; Ruben Manzo; Pierandrea Lo Nostro; Daniel Allemandi (26-34).
Alkyl vitamin C derivatives (ASC n ) combine in their structure a lipophilic and a hydrophilic moiety and exhibit properties of typical surfactant molecules. Self-assembly properties of ASC n depend on the length of n-alkyl fatty chain. ASC n start to aggregate at temperatures (CMT, Krafft point) in which the solubility reaches the critical micellar concentration (CMC). Above this temperature, ASC n can aggregate in micelles or gel phase, depending of alkyl side chain. Upon cooling, for less soluble derivatives (ASC12, ASC14 and ASC16) liquid-crystal structures named coagels are obtained. They are able to solubilized insoluble and unstable drugs, protect them from any possible aggressive environment and promote their permeation through skin. Besides, the rheological properties of the coagels would be adequate for topical administration of pharmaceutical. These systems possess very interesting properties making ASC n coagels promising pharmaceutical platforms for drug delivery. Results from investigations about all these properties are described and analyzed. Also, the perspectives of these systems as drug delivery systems are discussed.
Keywords: Vitamin C; Coagel; Nanostructures; Drug delivery;

Block copolymers for drug solubilisation: Relative hydrophobicities of polyether and polyester micelle-core-forming blocks by David Attwood; Colin Booth; Stephen G. Yeates; Chiraphon Chaibundit; Nágila M.P.S. Ricardo (35-41).
Published values of the critical micelle concentration are tabulated for diblock copolymers E m P n , E m B n , E m S n , E m L n , E m VL n and E m CL n , where E denotes a chain unit derived from ethylene oxide, P from propylene oxide, B from 1,2-butylene oxide, S from styrene oxide, L from dl-lactide, VL from γ-valerolactone and CL from ɛ-caprolactone, and the subscripts denote average chain lengths. Noting that log(cmc/mol dm−3 is proportional to the standard Gibbs energy of micellisation, the dependence of this quantity on hydrophobic block length (n) is explored for a given E-block length. Superposition of data allows ranking of the hydrophobicities of the chain units. The ratios relative to the least hydrophobic unit are: P : L : B : VL : S : CL = 1 : 4 : 6 : 10 : 12 : 12 Transitions in the slope of log(cmc) versus n are assigned to changes in the unimer-micelle equilibrium and related to the formation of unimolecular micelles and, at high values of n, to the completion of that process. The formation transition is seen in the plots for all the copolymers except the least hydrophobic, E m P n . The completion transition is seen in the plots for E m CL n and E m L n copolymers, as these alone include results for copolymers with very lengthy hydrophobic blocks.
Keywords: Solubilisation; Block copolymers; Critical micelle concentrations; Micelles;

Cyclodextrin/PEG based hydrogels for multi-drug delivery by Stefano Salmaso; Alessandra Semenzato; Sara Bersani; Pietro Matricardi; Fabio Rossi; Paolo Caliceti (42-50).
Cyclodextrin–PEG hydrogels were prepared by reaction of hexamethlyene isocyanate-activated β-cyclodextrins with 1.9 kDa NH2 ―PEG―NH2. The reaction was carried out in anhydrous dimethylsulfoxide by using 0.25:1, 0.33:1, 0.5:1, 0.67:1, 1:1, and 2:1 CD/PEG molar ratios. The addition of acetic acid to the reaction mixture was found to slow the cross-linking reaction, yielding homogeneous matrices. The mechanical characterization indicated that the elasticity of the matrices increased as the CD content in the hydrogel increased while the elongation was irrespective of the hydrogel composition. By incubation in water and ethanol, the hydrogels underwent complete swelling in 5–10 min. The water up-take increased logarithmically as the CD/PEG ratio decreased to reach a swelling degree of 800% (swollen hydrogel/dry hydrogel, w/w%). The ethanol uptake increased with a power correlation as the CD/PEG ratio decreased to reach a swelling degree of about 1000% with 0.25:1 CD/PEG hydrogel. Lysozyme, β-estradiol, and quinine were loaded by swell embedding. The lysozyme loading increased as the CD/PEG ratio decreased while the incorporation of β-estradiol and quinine displayed inverse correlation with respect to the CD/PEG ratio. The maximal incorporation (loaded drug/dry hydrogel, w/w%) for lysozyme, β-estradiol and quinine was 2, 0.6, and 2.4%, respectively. Lysozyme was quickly released from the matrices, and the release was faster as the CD/PEG ratio decreased. Also, β-estradiol and quinine release rates were inversely proportional to the CD/PEG ratio, but in these cases, the release profiles were strongly affected by the drug interaction with the hexamethylated β-cyclodextrins in the matrices.
Keywords: Hydrogel; Cyclodextrin; Polyethylene oxide; Drug delivery;

Amphiphilic block copolymers composed of prepoly(sebacic anhydride) and Pluronic-F68/F127 have been synthesized in different molar compositions via melt-polycondensation reaction. Poly(sebacic anhydride-co-PLF68/PLF127) thus formed was characterized by Fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC) and nuclear magnetic resonance spectroscopic (NMR) techniques. The amphiphilic block copolymers were used to prepare microspheres and to encapsulate nifedipine (NFD) by the solvent evaporation technique. Differential scanning calorimetry (DSC) was used to confirm the incorporation of Pluronic into polyanhydrides, while X-ray diffraction (XRD) was performed on the drug-loaded microspheres to investigate the crystalline nature of the drug after encapsulation. Scanning electron micrograph (SEM) pictures indicated spherical nature of the microspheres. Microspheres obtained were in the size range of 10–50 μm as measured by the laser particle size analyzer. In vitro release studies of NFD from poly(sebacic anhydride-co-Pluronic-F68/F127) microspheres performed in pH 7.4 phosphate buffer indicated sustained release rates of NFD at higher amounts of Pluronic in polyanhydride copolymers; there was no significant difference obtained between the release patterns of NFD from Pluronic-F68 and Pluronic-F127 copolyanhydride microspheres when same amount of Pluronics were used.
Keywords: Pluronic F68; Pluronic F127; Poly(sebacic anhydride); Nifedipine; Solvent evaporation; Microspheres;

5-ASA loaded chitosan–Ca–alginate microparticles: Preparation and physicochemical characterization by K. Mladenovska; O. Cruaud; P. Richomme; E. Belamie; R.S. Raicki; M.-C. Venier-Julienne; E. Popovski; J.P. Benoit; K. Goracinova (59-69).
The objective of the work was to prepare chitosan–Ca–alginate microparticles that can effectively deliver 5-ASA to the colon after peroral administration. For these requirements, a spray-drying technique was applied to 5-ASA/sodium alginate aqueous solution to obtain spherical particles having a mean diameter less than 10 μm. The microparticles formed were cross-linked and coated into solution of CaCl2 and chitosan to obtain stable microsystem. 1H NMR and UV–vis spectra of 5-ASA have shown no degradation when working in adequate conditions, such as light protection, freshly prepared solution and use of nitrogen to prevent the oxidative self-coupling of 5-ASA moieties. By imaging with SEM, acceptable spherical morphology was observed, but also flattened, disk-shaped particles of smooth surface and low porosity. CLSM imaging showed dominant localization of chitosan in the particle wall, while for alginate, a homogeneous distribution throughout the particle was observed giving the particles negative charge. In the FTIR spectra of 5-ASA loaded Ca–alginate microparticles the characteristic peaks of 5-ASA were not altered indicating no covalent interaction between the drug and the polymer. DSC and X-ray diffraction studies revealed that 5-ASA was molecularly dispersed within the chitosan–Ca–alginate microparticles during the production process.
Keywords: Alginate; Chitosan; 5-ASA; Microparticles; Spray-drying method; Physicochemical characterization;

Rate-modulating PHBHV/PCL microparticles containing weak acid model drugs by Fernanda S. Poletto; Eliézer Jäger; Maria I. Ré; Sílvia S. Guterres; Adriana R. Pohlmann (70-80).
In this work, we aimed to evaluate the influence of the proportions of poly(epsilon-caprolactone) (PCL) in the poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) blended microparticles on the drug release profiles of drug models and to determine the drug release mechanism. Diclofenac and indomethacin used as drug models showed encapsulation efficiencies close to 85%. The average diameters (122–273 μm) and the specific surface areas (26–120 m2  g−1) of the microparticles were dependent on the PCL concentration in the blends. Differential scanning calorimetry (DSC) analyses showed that the microparticle preparation process influenced the thermal behavior of PHBHV, as well as the glass transition temperature of PHBHV increased with the presence of indomethacin. The release profiles, described by a biexponential equation, showed sustained phase half-lives varying from 131 to 912 min (diclofenac) and from 502 to 6300 min (indomethacin) depending on the decrease of the PCL concentration. The product between the diffusion coefficient and the drug solubility in the matrix (DCs,m), which was proportional to the PCL concentration, was calculated by fitting the release data to the Baker–Lonsdale equation. The mechanism of release was mainly controlled by the drug diffusion and the drug release profiles were controlled by varying the PCL concentration systematically in the blended PHBHV/PCL microparticles.
Keywords: Drug release; Diffusion; Mathematical modeling; Microparticle; PHBHV; PCL;

Effects of 1,8-cineole on the dynamics of lipids and proteins of stratum corneum by Jorge Luiz Vieira dos Anjos; Diógenes de Sousa Neto; Antonio Alonso (81-87).
The interaction of a potent percutaneous penetration enhancer, 1,8-cineole, with the stratum corneum (SC) and DPPC membranes was investigated by electron paramagnetic resonance spectroscopy (EPR) of spin-labeled analogs of stearic acid (5-DSA) and androstanol (ASL). The EPR spectra of lipid derivatives spin probes structured in stratum corneum tissue of neonatal rat containing of 0.1–10% (v/v) 1,8-cineole in the solvent indicate an abrupt increase in membrane fluidity at around 1% 1,8-cineole. These spectra of stratum corneum membranes are characterized by the presence of two spectral components differing in mobility. Component 1 was attributed to the spin labels H-bonded to the headgroups, while component 2 possibly arose from spin labels H-bonded to water molecules or temporally non-hydrogen-bonded. With the addition of 1,8-cineole, the spin probes were transferred from the motionally more restricted component 1 to the more mobile component 2, suggesting that 1,8-cineole causes ruptures in the hydrogen-bonded network of the membrane–water interface, with consequent displacements of spin probes towards the hydrophobic core. 1,8-Cineole increased the rotational diffusion rates of component 2, whereas no significant mobility changes were observed in component 1. The EPR spectra of maleimide derivative spin label (6-MSL) covalently attached to stratum corneum proteins indicate that 1,8-cineole does not alter the dynamics of protein backbones. Instead, this terpene only increases the solvent's ability to ‘dissolve’ and mobilize the nitroxide side chain, which is in agreement with its low irritation response.
Keywords: Stratum corneum; EPR; Spin label; Lipid dynamics; Terpene; 1,8-Cineole;

Diffusion properties of model compounds in artificial sebum by Satyanarayana Valiveti; Guang Wei Lu (88-94).
Sebaceous glands secrete an oily sebum into the hair follicle. Hence, it is necessary to understand the drug partition and diffusion properties in the sebum for the targeted delivery of therapeutic agents into the sebum-filled hair follicle. A new method was developed and used for determination of sebum flux of topical therapeutic agents and other model compounds. The drug transport through artificial sebum was conducted using sebum loaded filter (Transwell®) as a membrane, drug suspensions as donor phases and HP-β-CD buffer solution as a receiver phase. The experiment was performed at 37 °C for 2 h. The results of the drug transport studies indicate that the flux (J sebum) through the artificial sebum is compound dependent and a bell-shaped curve was observed when log  J s versus alkyl side chain length of the compounds that proved to be different from the curves obtained upon plotting log  J skin versus clog  P for the same compounds, indicating the possibility to select appropriate compounds for sebum targeted delivery based on the differences in the skin flux and sebum transport profiles of the molecules.
Keywords: Artificial sebum; Flux; Permeability coefficient; Sebaceous gland; Hair follicle; Targeted delivery;

Phase characterization of indomethacin in binary solid dispersions with PVP VA64 or Myrj 52 by Xin Wang; Hector Novoa de Armas; Norbert Blaton; Armand Michoel; Guy Van den Mooter (95-100).
In the present study the properties of binary solid dispersions made up of PVP VA64, Myrj 52 and indomethacin (IMC) are studied and characterized. The solid dispersions were prepared by dissolving the materials in dichloromethane, followed by solvent evaporation under reduced pressure at 55 °C in a rotavapor. Binary solid dispersions were characterized by standard and modulated temperature differential scanning calorimetry (MTDSC), thermogravimetry (TGA) and X-ray powder diffraction (XRPD). XRPD analysis showed that the initial IMC was in its γ-form, and that it was transformed to the β-form (reported to be a solvate) together with an amorphous fraction in the solid dispersions. A mixture of the β-form and amorphous IMC was also obtained in the binary systems containing less than 30% polymer. IMC without adding polymer was subjected to the same experimental procedures as in the solid dispersions, and used as a model to characterize the solid-state transformations. The following order of transitions was observed: from the initial γ-form, the β-form was obtained together with an amorphous component, then the crystalline β-form transforms into the α-form which melts and recrystallizes into the most stable γ-form.
Keywords: PVP VA64; Myrj 52; Indomethacin; Polymorphism; MTDSC; X-ray powder diffraction; Solid dispersions;

Novel description of a design space for fluidised bed granulation by Tanja Lipsanen; Osmo Antikainen; Heikki Räikkönen; Sari Airaksinen; Jouko Yliruusi (101-107).
The physical measurements of a fluid bed granulator can be exploited in construction of an operating window, a design space, for process performance. The purpose of this study was to determine the influence of inlet air humidity changes on temperature in different parts of a granulator system, on fluidisation behaviour and on the particle size of the final granules. A humidifying setup was constructed on a bench-scale fluid bed granulator that enabled elevated humidity levels and sharp humidity changes of the inlet air. Ibuprofen granules were produced at the various inlet air humidity levels classified as low, intermediate and high. A novel fluidisation parameter was developed. The more improperly the particles were fluidising the smaller was the relationship of airflow rate and fan speed. Four different failure modes were identified and classified, based on the fluidisation parameter: over-fluidisation, risk of improper fluidisation, improper fluidisation and collapsed bed. It was possible to construct process trajectories for smooth fluidisation, which the optimal granulation process should follow.
Keywords: Fluid bed granulation; Fluidisation; Humidity; Design space; Process trajectory; Process analytical technologies (PAT);

Uniformity of poorly miscible powders determined by near infrared spectroscopy by Satu Virtanen; Osmo Antikainen; Jouko Yliruusi (108-115).
The objective of this work was to study with near infrared spectrometry (NIRS) the degree of mixing of poorly miscible binary mixtures of carbamazepine (CBZ) and α-lactose monohydrate (LMH). CBZ was cohesive and the particle size difference between CBZ (0.3 μm) and LMH (75 μm) was substantial. Mixed batches were measured directly in the mixing container with a fiber-optic probe. The spectral data were filtered by applying a novel automated selection technique during the NIRS measurement. The data analyses were performed with partial least squares modeling. Reference measurements were carried out with ultraviolet spectrophotometry. The results describe the degree of homogeneity at various depths. Some of the mixtures densified when the mixing speed increased. The densification of the batches was a source of error because it caused changes in the measuring geometry. The automated selection technique for the spectra reduced this problem. NIRS detected differences in the mixing degrees of mixtures and the method is suitable for mixing studies. However, the difference in the particle size of the materials and the densification caused problems to the measuring geometry. NIRS can be used at line, but the method requires accurate operation and method developing before it is useable.
Keywords: Powder mixing; Uniformity of powders; Near infrared spectroscopy; Particle size; Partial least squares modeling;

Effect of bee venom peptide–copolymer interactions on thermosensitive hydrogel delivery systems by Mingxi Qiao; Dawei Chen; Tangna Hao; Xiuli Zhao; Haiyang Hu; Xichen Ma (116-124).
The objectives of this study were to investigate the potential interactions between the model protein drug (bee venom peptide, BVP) and thermosensitive poly(dl-lactide-co-glycolide-b-ethyleneglycol-b-dl-lactide-co-glycolide) (PLGA–PEG–PLGA) copolymers and to examine the drug–copolymer interactions on the in vitro drug release and hydrogel degradation. The PLGA–PEG–PLGA copolymers were synthesized by ring-opening copolymerization of dl-lactide and glycolide with PEG as an initiator. Drug–copolymer co-precipitate blends were prepared and analyzed by Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) to characterize the specific interactions between drug and copolymer. For the better understanding the drug–copolymer interactions on drug release, insulin was selected for comparison. The release of the two protein drugs from the copolymer-based hydrogels and hydrogel degradation was studied at 37 °C under agitation. The results of FTIR and XRD indicated that the hydrogen bonding interactions existed between the N―H group of BVP and C=O group of the copolymers. The insulin and BVP released from the copolymer hydrogel over 15 and 40 days, respectively. The BVP–copolymer interactions retarded the BVP release rate and degradation of hydrogel, but did not significantly affect the biological activity of BVP. These results indicate that the drug–copolymer interactions need to be considered when attempting to use PLGA–PEG–PLGA hydrogels as sustained delivery carriers of protein or peptide drugs.
Keywords: Drug–copolymer interactions; Bee venom peptide; Hydrogen bonding; PLGA–PEG–PLGA; Thermosensitive hydrogels;

Evaluation of in vitro brain penetration: Optimized PAMPA and MDCKII-MDR1 assay comparison by Simone Carrara; Veronica Reali; Paola Misiano; Giulio Dondio; Chiara Bigogno (125-133).
Parallel artificial membrane permeability assay (PAMPA) is arising in ADMET screening as a powerful tool to determine the passive permeability of new potential chemical entities. In an attempt to set up a sensitive high throughput method to assess passive blood–brain barrier (BBB) penetration we focused our attention on the effect of solvent and the influence of phospholipids on the permeability in PAMPA. Moreover, the high throughput nature of the assay was maximized by decreasing the incubation time and performing the assay in a cassette mode. UPLC system coupled with a mass spectrometer enormously reduces the analytical time, contemporaneously increasing the sensitivity of the method. P app values obtained from PAMPA were compared to permeability values from MDCKII-MDR1 assay. Evaluation of the two in vitro models with in vivo data was performed to test the predicting capacity of the two methods. Their contemporary assessment was shown to be an helpful tool in understanding the prevalent mechanism of penetration through the BBB.
Keywords: BBB permeability screening; PAMPA; MDCKII-MDR1; High throughput screening; UPLC/MS;

Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability by Jong Soo Woo; Ming Guan Piao; Dong Xun Li; Dong-Sung Ryu; Jun Young Choi; Jung-Ae Kim; Jeong Hoon Kim; Sung Giu Jin; Dae-Duk Kim; Won Seok Lyoo; Chul Soon Yong; Han-Gon Choi (134-141).
To develop a hyaluronic microsphere with the improved oral bioavailability of poorly water-soluble cyclosporin A (CsA), the microspheres were prepared with varying ratios of sodium hyaluronate (HA)/sodium lauryl sulfate (SLS)/CsA using a spray-drying technique. The effects of HA and SLS on the dissolution and solubility of CsA in microspheres were investigated. The CsA-microsphere prepared with HA/SLS/CsA at the ratio of 4/2/1 gave the highest solubility and dissolution rate of CsA among those formulae tested. As solubility and dissolution rate of CsA were increased about 17- and 2-fold compared to CsA powder, respectively, this CsA-microsphere was selected as an optimal formula for oral delivery in rats. The CsA-microsphere and Sandimmun neoral sol® gave significantly higher blood levels compared with CsA powder alone. Moreover, the AUC, T max and C max values of CsA in CsA-microsphere were not significantly different from those in Sandimmun neoral sol® in rats, indicating that CsA–microsphere was bioequivalent to the commercial product in rats. Our results demonstrated that the CsA–microsphere prepared with HA and SLS, with improved bioavailability of CsA, might have been useful to deliver a poorly water-soluble CsA.
Keywords: Bioavailability; Cyclosporin A; Sodium hyaluronate; Sodium lauryl sulfate; Microsphere; Spray drying;

Effect of pH on the solubility and release of furosemide from polyamidoamine (PAMAM) dendrimer complexes by Bharathi Devarakonda; Daniel P. Otto; Anja Judefeind; Ronald A. Hill; Melgardt M. de Villiers (142-153).
The complexation of the practically insoluble drug furosemide (acidic pK a 3.22) with lower generation PAMAM dendrimers showed a significant release dependence on the ionization state of the drug. UV and FTIR studies suggested that the drug was localized in the interior of the dendrimer. The dendrimer amine, amide and ester groups, demonstrated pH-dependent ionization as did the drug carboxylic acid group and it was proven that the most efficient drug complexation was achieved in slightly acidic conditions (pH 4.0–6.0). At this pH, amide groups in the dendrimer cavities were at least partially ionized to expose a positive charge whilst the furosemide carboxylic acid ionized to great extent (pH > pK a) resulting in electrostatic complexation. Conversely, higher release rates were observed in acidic conditions (pH 1.2) where furosemide was virtually unionized, emphasizing the importance of the drug ionization state in the determination of drug release. Despite the complex interactions between the dendrimer and drug and its effects on release kinetics, the dendrimers resulted in higher solubility of the drug and contributed significantly to the array of available techniques to increase the solubility of poorly water-soluble drugs that are very abundant in industry today. Complexation with low generation PAMAM dendrimers (<generation 4) could provide opportunities to both increase drug solubility and tuning of the release profile for practically insoluble drugs.
Keywords: PAMAM dendrimer; Furosemide; Complexation; Ionization; Solubility; Release;

Encapsulation of moxifloxacin within poly(butyl cyanoacrylate) nanoparticles enhances efficacy against intracellular Mycobacterium tuberculosis by K.O. Kisich; S. Gelperina; M.P. Higgins; S. Wilson; E. Shipulo; E. Oganesyan; L. Heifets (154-162).
Macrophages in the lungs are the most important cell type supporting replication of Mycobacterium tuberculosis in humans. The objective of this study was to investigate whether the effect of moxifloxacin against M. tuberculosis residing in macrophages could be improved by encapsulation of the drug in the biodegradable nanoparticles, which are known to accumulate in macrophages upon intravenous administration. To accomplish this, moxifloxacin was encapsulated in poly(butyl cyanoacrylate) (PBCA) nanoparticles. Encapsulated moxifloxacin accumulated in macrophages approximately three-fold times more efficiently than the free drug, and was detected in the cells for at least six times longer than free moxifloxacin at the same extracellular concentration. Inhibition of intracellular M. tuberculosis growth with encapsulated moxifloxacin was achieved at the concentration of 0.1 μg/ml, whereas the same effect with free MX required a concentration of 1 μg/ml. Nanoparticles observed within the macrophage cytoplasm were distributed throughout the cytoplasm, sometimes in the vicinity of intracellular bacteria.
Keywords: Macrophage; Moxifloxacin; M. tuberculosis; Nanoparticles; Poly(butyl cyanoacrylate);

Solid lipid nanoparticles (SLN) of tretinoin: Potential in topical delivery by Kumar A. Shah; Abhijit A. Date; Medha D. Joshi; Vandana B. Patravale (163-171).
The objective of this investigation was to develop solid lipid nanoparticles (SLN) of tretinoin (TRE) with the help of facile and simple emulsification-solvent diffusion (ESD) technique and to evaluate the viability of an SLN based gel in improving topical delivery of TRE. The feasibility of fabricating SLN of TRE by the ESD method was successfully demonstrated in this investigation. The developed SLN were characterized for particle size, polydispersity index, entrapment efficiency of TRE and morphology. Studies were carried out to evaluate the ability of SLN in improving the photostability of TRE as compared to TRE in methanol. Encapsulation of TRE in SLN resulted in a significant improvement in its photostability in comparison to methanolic TRE solution and also prevented its isomerization. Furthermore, the skin irritation studies carried out on rabbits showed that SLN based TRE gel is significantly less irritating to skin as compared to marketed TRE cream and clearly indicated its potential in improving the skin tolerability of TRE. In vitro permeation studies through rat skin indicated that an SLN based TRE gel has permeation profile comparable to that of the marketed TRE cream.
Keywords: Tretinoin; Solid lipid nanoparticles (SLN); Emulsification-solvent diffusion; Photostability; SLN based gel; Draize patch test;

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