Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo

Objective: To formulate and evaluate solid-reversed-micellar-solution (SRMS)-based solid lipid microparticles (SLMs) for intramuscular administration of gentamicin.

Methods: SRMS formulated with Phospholipon® 90G and Softisan® 154 were used to prepare gentamicin-loaded SLMs. Characterizations based on size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release of gentamicin from the SLMs was performed in phosphate buffer while in vivo release studies were conducted in rats.

Results: Maximum EE% of 90.0, 91.6 and 83.0% were obtained for SLMs formed with SRMS 1:1, 1:2 and 2:1, respectively. Stable, spherical and smooth SLMs of size range 9.80?±?1.46?µm to 33.30?±?6.42?µm were produced. The release of gentamicin in phosphate buffer varied widely with the lipid contents. Moreover, significant (p?<?0.05) amount of gentamicin was released in vivo from the SLMs.

Conclusion: SRMS-based SLMs would likely offer a reliable means of delivering gentamicin intramuscularly.     

Sustained release indomethacin-loaded solid lipid microparticles based on solidified reverse micellar solution (SRMS): in vitro and in vivo evaluation

Solidified reverse micellar solutions (SRMS) were formulated using phospholipid (Phospholipon 90H) and triglyceride (Softisan 154) in the ratios of 1:1, 2:1 and 1:2, respectively. SLMs were prepared by melt homogenization technique. Characterization based on yield, mean particle diameter and morphology, pH, thermal analysis and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release was carried out in simulated intestinal fluid (SIF, pH 7.5), while the anti-inflammatory and ulcerogenic properties were studied using rats. From the results, the mean particle diameter of SLMs ranged from 2.19 ± 0.05 μm to 20.77 ± 0.03 μm. Maximum EE% of 96, 93 and 94 % were obtained and showed significant variation within the batches (p < 0.05). The release profile of indomethacin-loaded SLMs showed about 82-99 % drug release at 13 h. Indomethacin-loaded SLMs showed good anti-inflammatory and gastro-protective effects, and could be formulated for once-daily administration, either orally or parenterally, under controlled conditions.     

Formulation of novel sustained release rifampicin-loaded solid lipid microparticles based on structured lipid matrices from Moringa oleifera

Abstract

Objectives: To formulate sustained release rifampicin-loaded solid lipid microparticles (SLMs) using structured lipid matrices based on Moringa oil (MO) and Phospholipon 90G (P90G).

Methods: Rifampicin-loaded and unloaded SLMs were formulated by melt homogenization and characterized in terms of particle morphology and size, percentage drug content (PDC), pH stability, stability in simulated gastric fluid (SGF, pH 1.2), minimum inhibitory concentration (MIC) and in vitro release. In vivo release was studied in Wistar rats.

Results: Rifampicin-loaded SLMs had particle size range of 32.50?±?2.10 to 34.0?±?8.40?μm, highest PDC of 87.6% and showed stable pH. SLMs had good sustained release properties with about 77.1% release at 12?h in phosphate buffer (pH 6.8) and 80.3% drug release at 12?h in simulated intestinal fluid (SIF, pH 7.4). SLMs exhibited 48.51% degradation of rifampicin in SGF at 3?h, while rifampicin pure sample had 95.5% degradation. Formulations exhibited MIC range of 0.781 to 1.562, 31.25 to 62.5 and 6.25 to 12.5?μg/ml against Salmonella typhi, Escherichia coli, and Bacillus subtilis respectively and had higher in vivo absorption than the reference rifampicin (p?<?0.05).

Conclusion: Rifampicin-loaded SLMs could be used once daily for the treatment tuberculosis.     

Solid lipid micro-dispersions (SLMs) based on PEGylated solidified reverse micellar solutions (SRMS): a novel carrier system for gentamicin

Abstract

The purpose of this study was to formulate and evaluate novel PEGylated solidified reverse micellar solutions (SRMS)-based solid lipid microparticles (SLMs) for improved delivery of gentamicin. Lipid matrix (SRMS) [consisting of 15% w/w Phospholipon® 90G (P90G) in 35% w/w dika wax (Irvingia gabonensis) was formulated and characterized by differential scanning calorimetry (DSC). SLMs were formulated by melt-emulsification using the SRMS, PEG 4000 and gentamicin (1.0, 2.0, 3.0% w/w), and their physicochemical as well as pharmacokinetic parameters determined. In vitro permeation of gentamicin from the SLMs through artificial membrane (0.22?μm pore size) was carried out using Franz’s cell and phosphate-buffered saline (PBS, pH 7.4) as acceptor medium, while bioevaluation was performed using clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Stable and irregularly-shaped gentamicin-loaded SLMs of size range 34.49?±?2.56 to 53.52?±?3.09?µm were obtained. The SLMs showed sustained drug permeation and exhibited time-dependent and capacity-limited bioactivity. Overall, SLMs containing 2% w/w SRMS, 3% w/w gentamicin and PEG 4000 entrapped the highest amount of drug, gave highest IZD against the test organisms and highest permeation flux (5.239?μg/cm².min) and permeation coefficient (1.781?×?10^?6?cm/min) within 420?min, while pure gentamicin gave the least. Preliminary in vivo pharmacokinetic studies also showed an AUC-₂₄ of 1507?µg/h/ml for the optimized formulation, while that of oral drug solution was 678?µg/h/ml. This showed a 2.2-fold increase in the systemic bioavailability of gentamicin from the optimized formulation. PEGylated SRMS-based SLMs prepared with heterolipid from Irvingia gabonensis would likely offer a reliable delivery system for gentamicin.     

Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation

Objective: To formulate sustained-release diclofenac potassium-loaded solid lipid microparticles (SLMs) based on solidified reverse micellar solution (SRMS) and to evaluate the in vitro and in vivo properties.

Methods: SRMS consisting of mixtures of Phospholipon® 90H and Softisan® 154 were used to formulate diclofenac potassium-loaded SLMs. Characterization based on the particle size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release was carried out in simulated intestinal fluid (pH 7.5). Anti-inflammatory and ulcerogenic properties were studied using rats.

Results: Maximum EE% of 95%, 94% and 93% were obtained for SLMs formulated with SRMS 1:1, 2:1 and 1:2, respectively. In vitro release showed about 85–90% drug release at 13?h. Diclofenac potassium-loaded SLMs showed good anti-inflammatory and gastro-protective properties.

Conclusion: Diclofenac potassium-loaded SLMs based on SRMS could be used orally or parenterally under controlled conditions, for once daily administration.     

Formulation in vitro and in vivo evaluation of SRMS-based heterolipid-templated homolipid delivery system for diclofenac sodium

The sole objective of this work was to design successful dosage oral forms of diclofenac sodium (DiNa)-loaded solid lipid microparticles (SLM) based on solidified reverse micellar solution (SRMS). Hot homogenization technique was employed to prepare DicNa SLM using a mixture goat fat and Phospholipon® 90?G as lipid matrix and Tween®-80 as mobile surfactant. Characterization based on percentage yield, morphology, particle size, zeta potential, percentage encapsulation, pH and stability of SLMs were investigated. Anti-inflammatory, gastrointestinal tract (GIT) sparing effect and pharmacokinetics were carried out in rat model after oral administration. Results showed that the SLMs were spherical and smooth. The optimized formulation (SLM-4) had particle size of 79.40?±?0.31?µm, polydispersity index of 0.633?±?0.190, zeta potential of ?63.20?±?0.12?mV and encapsulation efficiency of 91.2?±?0.1% with good stability after 8?months of storage. The DicNa SLM had sustained release effect with good anti-inflammatory activity. Higher and prolonged plasma DicNa concentration was shown by the SLM-4 compared to pure drug and a conventional sample. These studies demonstrate that DicNa-loaded SLM based on SRMS could be a promising oral formulation for enhanced bioavailability, pharmacologic activity and gastrointestinal sparing effect of the NSAID, DicNa.     

Formulation,in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles

Abstract

Context: Formulation, characterization, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles (SLMs).

Objective: The objective of the study was to formulate and evaluate halofantrine-loaded SLMs.

Materials and methods: Formulations of halofantrine-loaded SLMs were prepared by hot homogenization and thereafter lyophilized and characterized using particle size, pH stability, loading capacity (LC) and encapsulation efficiency (EE). In vitro release of halofantrine (Hf) from the optimized SLMs was performed in SIF and SGF. In vivo study using Peter’s Four day suppressive protocol in mice and the mice thereafter subjected to histological studies in kidney and liver.

Results: Results obtained indicated that EE of 76.32% and 61.43% were obtained for the SLMs containing 7% and 3% of Hf respectively. The SLMs loaded with 3% of Hf had the highest yield of 73.33%. Time-dependent pH stability analysis showed little variations in pH ranging from 3.49?±?0.04 to 4.03?±?0.05.

Discussion: The SLMs showed pH-dependent release profile; in SIF (43.5% of the drug for each of H₂ and H₃) compared with SGF (13 and 18% for H₂ and H₃ respectively) after 8?h. The optimized SLMs formulation and Halfan® produced a percentage reduction in parasitemia of 72.96% and 85.71% respectively. The histological studies revealed that the SLMs formulations have no harmful effects on the kidney and liver.

Conclusion: SLMs formulations might be an alternative for patients with parasitemia as there were no harmful effects on vital organs of the mice.     

Evaluation of solid lipid microparticles produced by spray congealing for topical application of econazole nitrate

Objectives The aims of this study were to evaluate the suitability of the spray congealing technique to produce solid lipid microparticles (SLMs) for topical administration and to study the skin permeation of a drug from SLMs compared with solid lipid nanoparticles (SLNs). Methods Econazole nitrate was used as model drug and Precirol ATO 5 as the lipidic carrier. SLMs and SLNs were both prepared at 5: 1, 10: 1 and 12.5: 1 lipid: drug weight ratios and characterised in terms of particle size, morphology, encapsulation efficiency and chemical analysis of the particle surface. SLMs and SLNs were also incorporated into HPMC K 100M hydrogels for ex‐vivo drug permeation tests using porcine epidermis. Key findings SLMs had particle sizes of 18–45 μm, while SLNs showed a mean diameter of 130–270 nm. The encapsulation efficiency was 80–100%. Permeation profiles of econazole nitrate were influenced by both particle size (significant difference until 9 h) and the amount of lipid. Conclusions The results confirm the usefulness of SLNs as carriers for topical administration and suggest the potential of SLMs for the delivery of drugs to the skin.     

Preparation and characterization of textile-based carrier systems for anal fissure treatment

Anal fissure is common and painful disease of anorectum. In this study, microparticles containing nifedipine and lidocaine HCl were prepared by spray drying and applied to bio-degradable and bio-stable tampons. Characterization of microparticles was determined by visual analyses, mass yield, particle size measurement, encapsulation efficiency, drug loading and in vitro drug release. Mass yield was between 5.5 and 45.9%. The particle size was between 15.1 and 26.8?µm. Encapsulation efficiency were 96.142?±?5.931 and 85.571?±?3.301; drug loading were 65.261?±?3.914% and 37.844?±?4.339% of L2 and N1, respectively. Well-separated, mainly spherical microparticles with suitable properties were obtained. Optimum microparticles were applied to tampons. Physical properties and visual characteristics of tampons were investigated before and after binder application. In vitro drug release from tampons were also examined. According to the results, textile-based carrier systems loaded microparticles containing nifedipine and lidocaine HCl will be an effective and promising alternative for current anal fissure treatment.     

Formulation and characterization of catalase in albumin microspheres

Abstract

Catalase in albumin microspheres were formulated for intravenous administration to antagonize the effects of over-production of reactive oxygenated species (ROS) such as hydrogen peroxide (H₂O₂) in septic shock. The aim was to increase effective half-life of catalase and take advantage of the phagocytic uptake of the encapsulated catalase by the vascular endothelium. Catalase microspheres were prepared by spray-drying. The microspheres were evaluated for particle size, particle shape and surface morphology by scanning electron microscopy (SEM), drug encapsulation efficiency, chemical stability, thermal stability and in vitro drug release characteristics. The microspheres had a mean particle size of 4.7 ± 2 µm, optimal for phagocytic uptake, as demonstrated by Makino et al. SEM revealed that microspheres were spherical with smooth surface morphology. An encapsulation efficiency of 91.5 ± 3% was achieved and the encapsulated catalase was chemically and thermally stable. Application of in vitro drug release data to the Higuchi kinetic equation indicated matrix diffusion-controlled catalase release from albumin microspheres.     

The protective effect of liquorice components and their derivatives against gastric ulcer induced by aspirin in rats

Abstract— We have examined the protective effect of liquorice or its derivatives against gastric ulcer induced by aspirin. A granular mixture of aspirin alone and coated with liquorice or its derivatives including the deglycyrrhized form, a high glycyrrhized form, carbenoxolone, and enoxolone were studied. Aspirin coated with liquorice reduced the number and size of ulcers, reducing the ulcer index from 1·5±0·12 to 0·5 ± 0·12 and the incidence from 96% to 46%. Coating with derivatives was less effective (ulcer index, 0·70–0·94; incidence 62–76%).     

Microsponge based drug delivery system for augmented gastroparesis therapy: Formulation development and evaluation

The intention behind the present work was to develop a microsponge based novel dosage form for sustained delivery of domperidone. Quasi-emulsion solvent diffusion method was employed using Eudragit RS-100 with various drug–polymer ratios for the preparation of microsponges. For optimization purposes, several factors which affect microparticles' physical properties were investigated. Characterization techniques followed for the formed microsponges were DSC, FTIR, SEM, XRD and particle size analysis, along with morphology, drug loading and in vitro drug release. It was found that there were no chemical interactions between drugs and polymers used as per DSC and FTIR results. The drug–polymer ratio showed remarkable impact on drug content, encapsulation efficiency and particle size. SEM micrographs revealed that microsponges were spherical in shape with porous surface, and had 104 ± 0.22 µm mean particle size. The microsponges were then loaded in capsules followed by in vitro drug release study; which depicted that microsponges with drug–polymer ratio of 1:2 were more proficient to give extended drug release of 76.38% at the end of 8 h, superior in contrast to conventional marketed formulation Domstal^®, which got exhausted incredibly earlier by releasing 82.57% drug at the end of ½ h only. Hence, the developed microsponge based formulation of domperidone would be an expectant, promising substitute to conventional therapy of gastroparesis, emesis and alike gastric ailments.     

Effect of raw material variability of glipizide on the in vitro dissolution rate and in vivo bioavailability performance: The importance of particle size

The objective of this study was to understand the impact of active pharmaceutical ingredients (API) particle size on a re-developed generic product of glipizide and to improve its formulation so that it exhibits bioequivalent to that of the reference listed drug (RLD). Two commercial batches of APIs (API-1 and API-2) with the same polymorphism and one batch of home-made APIs (API-3) with super-small particle size were used in the present study. The in vitro dissolution profiles of the tested formulations were compared with the RLD in a series of dissolution media. Then, the impact of particle size on in vivo absorption was evaluated in Beagle dogs. Compared with the RLD, formulation A with larger API size showed slower dissolution in pH 6.0 and 7.4 medium, resulting bioinequivalent with the RLD. Conversely, formulation B with smaller API size demonstrated similar in vitro dissolution profiles with the RLD and thus exhibited bioequivalent in the present study. Furthermore, formulation C with super small particle size still exhibited identical oral absorption although rapid dissolution was observed in the tested condition. Herein, it indicated that 2–5 µm might be defined as the “inert size range” of glipizide for ensuring the bioequivalence with the RLD. The results in the present study might help to obtain a better understanding of the variability in raw materials for oral absorption, develop a bioequivalent product and thus post-market quality control.     

Preparation and Evaluation of Controlled Release Microparticles for Respiratory Protein Therapy

A series of microparticle formulations, designed for controlled release pulmonary therapy, were evaluated in terms of their physical properties, aerosol performance, lung epithelial cell toxicity, and controlled release profile. A protein, bovine serum albumin (BSA) was chosen as a model macromolecule active ingredient which was coprocessed, using spray drying, with varying concentrations of the release modifier, polyvinyl alcohol (PVA). The spray dried microparticles were tested for their physico-chemical characteristics (e.g., size distribution, morphology and density), in vitro aerosolisation performance using a 5-stage Marple Miller Impactor (MMI) and in vitro release profiles by a custom-built diffusion cell (in 100 mL phosphate buffer pH 7.4). The toxicity of PVA on lung epithelial cells was investigated using a human alveolar basal epithelium A549 cell line. Analysis of the particle size data indicated that all the spray dried BSA/PVA samples had similar size distributions with a median particle diameter (d_0.5) across all samples of 2.79 ± 0.11 µm. All formulations had relatively good aerosolisation performance when compared to conventional dry powder inhalation (DPI) formulations although increasing PVA percentage had a negative effect on the aerosol performance in vitro. Analysis of the difference and similarity factors for the release profiles indicated significant differences with respect to PVA concentration. Furthermore, cell toxicity analysis indicated PVA to have limited effect on cell viability after 24 h exposure. A series of protein-based inhalation formulations have been developed and tested, and shown to be suitable for controlled release in the respiratory tract. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2709–2717, 2009     

Lipid-core nanocapsules are an alternative to the pulmonary delivery and to increase the stability of statins

Abstract

Aims: Lipid-core nanocapsules (LNCs) loaded with simvastatin (SV, SV-LNC) or lovastatin (LV, LV-LNC) were formulated for pulmonary administration.

Methods: The LNC suspensions were characterized physicochemically, their stability was evaluated, and drug delivery by the pulmonary route was tested in vitro.

Results: The loaded LNCs had a particle size close to 200?nm, a low polydispersity index, and a zeta potential around ?20?mV. The encapsulation efficiency was high for SV (99.21?±?0.7%) but low for LV (20.34?±?1.2%). SV release from nanocapsules was slower than it was from SV in solution, with a monoexponential release profile, and the drug emitted and aerosol output rate was higher for SV-LNCs (1.58?µg/s) than for SV in suspension (0.54?µg/s).

Conclusions: SV-LNCs had a median aerodynamic diameter of 3.51?µm and a highly respirable fraction (61.9%), indicating that nanoparticles are a suitable system for efficient delivery of simvastatin to the lung.     

Protective Effect of Aegle marmelos Fruit in Gastrointestinal Dysfunction in rats

The effect of the ethanol extract of the unriped fruits of Aegle marmelos Correa was assessed on experimentally induced diarrhoea and gastric ulceration in rats. The extract (50, 100 and 200?mg/kg, p.o.) exhibited a dose-dependent decrease in the intestinal propulsion from 61.79–39.32% which is equivalent to 38.21–60.68% intestinal propulsion inhibition (control 58.3 ± 3.4 inhibition, P < 0.5 to P < 0.001) and caused a dose-dependent decrease in the total number of faecal matter in castor oil-induced diarrhoea (control 70, reduced to 51 and 42 at 100 and 200?mg/kg extract, p.o.). Further, yohimbine, a α₂ adrenoreceptor blocker, attenuated the antidiarrhoeal effect of the extract in a dose of 200?mg/kg to 17.14%, and diphenoxylate by 74.28%. The extract also reduced the ulcer index induced by ethanol (control 18.7 ± 4.4, 34.22–72.73% protection), aspirin (control 22.6 ± 3.4, 36.73–81.42% protection) and cold restraint stress (control 23.8 ± 3.2, 56.72% and 81.51% protection). Further study on tissue lipid peroxidation was significantly increased (P < 0.001) as evidenced by accumulation of malondialdehyde in cold restraint stress ulcers. Administration of A. marmelos (100 and 200?mg/kg), cimetidine 50?mg/kg and reduced glutathione (150?mg/kg) prior to cold restraint stress causes significant decrease in ulcer index and lipid peroxidation (P < 0.01 to P < 0.001). The result showed that A. marmelos had significant antidiarrhoeal and ulcer protective activity by scavenging the reactive oxygen species on the cold restraint stress-induced gastric damage.     

Fabrication and evaluation of lipid nanoparticulates for ocular delivery of a COX-2 inhibitor

Context: The unique physiological limitations of the eye have been assigned as reason of low bioavailability by conventional drug delivery systems. There is need of such drug carriers, which ensure improved bioavailability as well as patient compliance upon instillation into the eye.

Objective: The present investigation deals with development of solid lipid nanoparticles (SLNs) containing celecoxib (CXB) for treatment of ophthalmic inflammations.

Materials and methods: The SLNs were formulated by melt-emulsion sonication and low temperature-solidification process and evaluated for particle size, surface morphology, physicochemical properties, percentage drug incorporation efficiency, in vitro drug release, in vitro trans-corneal permeation, in vivo efficacy in ocular inflammation, stability study and gamma scintigraphy study to assess the residence of solid lipid nanoparticles over ocular surfaces.

Results: The SLNs were spherical and the optimized formulation had particle size of 198.77?±?7.5?nm, which is quite suitable for ocular applications. The maximum entrapment efficiency of 92.46?±?0.07% was achieved for formulation SLN 20. The permeation across the cornea was also significantly better than aqueous suspension (8.21?±?0.67 versus 4.61?±?0.71) at p?<?0.05.

Discussion and conclusion: The SLN formulations demonstrated improved performance of entrapped CXB while mitigating the key parameters of ocular inflammation in rabbits. The particulate formulations have exhibited prolonged retention over ocular surfaces as evident from results of gamma scintigraphy using ^99mTc labeled SLNs.     

Development of a topical ointment of betamethasone dipropionate loaded nanostructured lipid carrier

The purpose of this study was to design an innovative topical ointment containing betamethasone dipropionate loaded nanostructured lipid carrier (BD-NLC) for the treatment of atopic dermatitis (AD). BD-loaded NLC was produced with precirol ATO 5 and oleic oil (OA) by melt emulsification method. Effects of surfactant concentration, amount of solid lipid and liquid lipid on skin retention and skin penetration were investigated by in vitro percutaneous permeation experiment. The optimized BD-NLC showed a homogeneous particle size of 169.1 nm (with PI = 0.195), negatively charged surface (−23.4 mV) and high encapsulation efficiency (85%). Particle morphology assessed by TEM revealed a spherical shape. In vitro skin permeation study was carried out to investigate the percutaneous behaviors of W/O ointment with BD-NLC and Carbopol emulgel ointment with BD-NLC. W/O ointment with BD-NLC showed high skin retention (35.43 µg/g) and low penetration (0.87 µg/ml). In vitro drug release studies were carried out to demonstrate the drug releasing properties of the two ointments. W/O ointment with BD-NLC showed an advantage for skin retention as it was better for drug release. The tissue distribution test suggested that BD distribution was skin > muscle > blood. Self-made topical ointment in mice showed no skin irritation. The animal experiments indicated that BD-loaded NLC ointment was effective and safe for topical use.     

In vitro evaluation of α-lipoic acid-loaded lipid nanocapsules for topical delivery

This study aimed at in vitro evaluation of α-lipoic acid-loaded lipid nanocapsules for topical delivery, which was prepared by hot high-pressure homogenisation. Stable particles could be formed and particle size was 148.54?±?2.31?nm with polydispersity index below 0.15. Encapsulation efficiency and drug loading of α-lipoic acid were 95.23?±?0.45% and 2.81?±?0.37%. Antioxidant study showed α-lipoic acid could be protected by lipid nanocapsules without loss of antioxidant activity. Sustained release of α-lipoic acid from lipid nanocapsules was obtained and cumulative release was 62.18?±?1.51%. In vitro percutaneous study showed the amount of α-lipoic acid distributed in skin was 1.7-fold than permeated. Cytotoxicity assay and antioxidant activity on L929 cells indicated this formulation had low cytotoxicity and ability of protecting cells from oxidative damage within specific concentration. These studies suggested α-lipoic acid-loaded lipid nanocapsules could be potential formulation for topical delivery.     

Testosterone solid lipid microparticles for transdermal drug delivery. Formulation and physicochemical characterization

Purpose: The main objective of the study was to formulate and characterize testosterone (TS) solid lipid microparticles (SLM) to be applied as a transdermal delivery system.

Methods: Testosterone SLMs were formulated using an emulsion melt homogenization method. Various types and concentrations of fatty materials, namely glyceryl monostearate (GM), glyceryl distearate (GD), stearic acid (SA) and glyceryl behanate (GB) were used. The formulations contained 2.5 or 5?mg TS?g^?1. Morphology, particle size, entrapment efficiency (EE), rheological properties and thermal behaviour of the prepared SLM were examined. In vitro release characteristics of TS from various prepared SLM were also evaluated over 24?h using a vertical Franz diffusion cell. In addition, the effect of storage and freeze-drying on particle size and release pattern of TS from the selected formulation was evaluated.

Results: The results indicated that the type of lipid affected the morphology and particle size of SLM. A relatively high drug percentage entrapment efficiency ranging from 80.7–95.7% was obtained. Rheological studies showed plastic flow characteristics of the prepared formulations. DSC examination revealed that TS existed in amorphous form in the prepared SLM. Release studies revealed the following rank order of TS permeation through cellophane membrane after application of various formulations: 5% GM?<?5% GD?<?5% SA?<?5% GB?<?2.5% GM?<?2.5% SA?<?10% GD?<?10% GB. The drug permeation through excised abdomen rat skin after application of 10% GB–2.5?mg TS?g^?1 SLM was lower than that permeated through cellophane membrane. Moreover, SLM containing 10% GB–2.5?mg TS?g^?1 stored at 5°C showed good stability as indicated by the release study and particle size analysis. Trehalose showed high potential as a cryoprotectant during freeze drying of the selected SLM formulation.

Conclusions: The developed TS SLM delivery system seemed to be promising as a TS transdermal delivery system.