Topical gel of Metformin solid lipid nanoparticles: a hopeful promise as a dermal delivery system

The aim of the present study was to enhance the skin delivery of metformin by making solid lipid nanoparticles containing metformin using the ultra-sonication method. To achieve the optimum skin delivery for metformin, the effects of the ratio of two surfactants (Tween:Span) on nanoparticles properties and their performance were investigated. Photon correlation spectroscopy, scanning electron microscopy (SEM), Powder X-ray Diffractometer (PXRD), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to characterize the solid state of metformin in solid lipid nanoparticles. Generally, the particle size of nanoparticles decreased by the addition of co-emulsifier (Span®60). Results showed that all formulations made by binary mixtures of surfactants had low particle size, low Polydispersity index and high zeta potential. It was interesting to note that the smallest nanoparticles (203.8 ± 15.356) was obtained when the HLB of the binary surfactants (HLB of 11.67) was closer to the HLB of beeswax (HLB of 12) used in the preparation of SLN. It was also found that by decreasing the HLB of the system from 14.9 to 10.06 the zeta potential of SLNs increased from −0.651 ± 0.315 to −6.18 ± 0.438 mV. But, a further reduction in the HLB from 10.06 to 8.45 caused a reduction in the zeta potential from −6.18 to −3.596 ± 0.255. Results showed that the highest entrapment efficiency of 45.98 ± 9.20% was obtained for formulation with larger particle size and with the highest HLB value (HLB 14.9). DSC study showed that metformin in SLN is in an amorphous form. FT-IR spectra of Met-SLN showed that the prominent functional groups existed in the formulations which could be an indication of good entrapment of metformin in a lipid matrix. FT-IR results also ruled out any chemical interaction between the drug and the excipients. The amounts of metformin detected in the skin layers and the receptor chamber at all sampling times were higher for nanogel compared to metformin gel. This is an indication of a better performance of Metformin nanogel ex-vivo and could be developed further for clinical studies

Liquisolid compact: Effect of Propylene glycol and Tween80 on atorvastatin release from tablet matrices containing Eudragit RSPO

Introduction: Liquisolid system has been used to increase the dissolution rate of hydrophobic drugs. Since drug solubility play an important role in drug release profile, using appropriate solvent can lead the system to become sustain release. The aim of this study was to investigate the effect of different liquid vehicles and Eudragit RSPO on release characteristics of atorvastatin as a hydrophobic drug. Methods and Results: Several Liquisolid compacts with Propylene glycol and tween80 with different drug solvent ratio was prepared. The ratio of the carrier material (Eudragit RSPO: microcrystalline cellulose, (60:40)), for coating material (silica) was 2 in all formulations. To evaluate any interaction between atorvastatin and the other components, the differential scanning calorimeter (DSC) and Fourier transform infrared spectroscopy (FTIR) was used. Atorvastatin Liquisolid compacts containing Propylene glycol and tween80 as liquid vehicle increased dissolution rate of drug from 23.75±0.33 (in conventional matrix formulation) to 38.66±1.77 and 99.95±4.2 respectively, in first 480 minute. By increasing the ratio of tween80 to drug from 1:1 to 4:1 reduced drug retardation was seen, consequently the release percentage increased from 60.50±3.1 to 99.95±4.2. This was contrary to propylene glycol drug formulation. The resultant difference in effect of formulations was probably due to more solubility of atorvastatin in tween80 (26.77 g/100ml) in comparison to Propylene glycol (11.65 g/100ml). It was observed that a slight change on carrier (55.66 increased to 57.54%) and drug percentage (3.15% decreased to 2.59%) in formulation with Tween80:drug ratio (4:1), presented more retardation effect so that release percentage decreased from 99.95±4.2 to 75.92± 2.20. All formulations had hardness and friability between (35.6±0.57 - 43.4±1.14) N and (0.67% - 1.3%), respectively. The DSC, FTIR and X-ray evaluations revealed no interaction between drug and excipients.  Conclusions: The liquisolid compacts with the suitable carrier can be promising technique to sustain release drugs, in addition, type of nonvolatile solvent has an important effect on liquisolid release profile

The design of naproxen solid lipid nanoparticles to target skin layers

The aim of the current investigation was to produce naproxen solid lipid nanoparticles (Nap-SLNs) by the ultrasonication method to improve its skin permeation and also to investigate the influence of Hydrophilic-lipophilic balance (HLB) changes on nanoparticles properties. The properties of obtained SLNs loaded with naproxen were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). FT-IR was also used to investigate any interaction between naproxen and the excipients used at the molecular level during the preparation of the SLNs. The performance of the formulations was investigated in terms of skin permeation and also the retention of the drug by the skin. It was found that generally, with increasing the lipid concentration, the average particle size and polydispersity index (PDI) of SLNs increased from 94.257 ± 4.852 nm to 143.90 ± 2.685 nm and from 0.293 ± 0.037 to 0.525 ± 0.038 respectively. The results also showed that a reduction in the HLB resulted in an increase in the PDI, particle size, zeta potential and entrapment efficiency (EE %). DSC showed that the naproxen encapsulated in the SLNs was in its amorphous form. The peaks of prominent functional groups of naproxen were found in the FT-IR spectra of naproxen-SLN, which confirmed the entrapment of naproxen in the lipid matrix. FT-IR results also ruled out any chemical interaction between drug and the chemicals used in the preparation of SLNs. The amount of naproxen detected in the receptor chamber at all the sampling times for the reference formulation (naproxen solution containing all surfactants at pH 7.4) was higher than that of the Nap-SLN8 formulation. Nap-SLN8 showed an increase in the concentration of naproxen in the skin layer with less systemic absorption. This indicates that most of the drug in Nap-SLN8 remains in the skin which can reduce the side effect of systemic absorption of the drug and increases the concentration of the drug at the site of the action

An emerging technology in lipid research for targeting hydrophilic drugs to the skin in the treatment of hyperpigmentation disorders: kojic acid-solid lipid nanoparticles

AbstractKojic acid (KA) as tyrosinase inhibitor shows insufficient skin penetration and several adverse events due topical administration. KA solid lipid nanoparticles (KA-SLNs) were prepared using high speed homogenisation followed by ultra-probe sonication method for improve its effectiveness.KA-SLNs was optimised by Glyceryl mono-stearate (GMS) and Cholesterol (Chol) as lipid excipients and span 60 (SP 60) and Tween 20 (Tw 20) as co-emulsifiers (particle size 156.97 ± 7.15 nm, encapsulation efficiency 59.02 ± 0.74%, drug loading 14.755 ± 1.63%, polydispersity index (PDI) of 0.388 ± 0.004 and zeta potential (ZP) of -27.67 ± 1.89 mV). Optimum formulation (KA-SLN3 dispersion) was stable at 4 and 25 °C for 3 months. Also, TEM image confirmed these results. The results of XRD, DSC and ATR-FTIR analysis indicated that KA was well encapsulated within the SLNs either in molecularly dispersed state and stabilised in amorphous form and there was no chemical interaction between drug and other ingredients. Controlled release was achieved with this formulation. KA-SLN3 dispersion have more tyrosinase inhibition potency in comparison with pure KA. Also, the results of the ex vivo and in vitro percutaneous absorption show that KA-SLN3 dispersion improved percutaneous delivery of KA as a promising and potential novel topical preparation and might open new avenues for treatment of hyperpigmentation disorders

The effect of Plantago major seed mucilage combined with carbopol on the release profile and bioadhesive properties of propranolol HCl buccoadhesive tablets

Buccoadhesive drug delivery systems have distinct advantages in comparison with oral administration. Plant exudates like gum or mucilage are being studied for their use as pharmaceutical adjuvant. The aim of this study is to evaluate the properties of the Plantago major seed mucilage as a mucoadhesive agent and propranolol hydrochloride is chosen as a model drug. Mucoadhesive tablets of propranolol hydrochloride were formulated by combination of two mucoadhesive polymers include Carbopol 934P and Plantago major mucilage, and properties such as in vitro drug release, swelling, erosion, mucoadhesive force were studied. The results show increase in bioadhesive strength and decrease in release rate with increase in percent of Carbopol 934P, as F13 (containing Carbopol 934P alone) and F8 (containing mucilage alone) show the highest bioadhesive strength and highest release rate respectively and these results were matched to swelling results which decrease in swelling of matrices results in decrease in bioadhesion. Matrices with both Plantago major mucilage and Carbopol have the optimum drug release in bioadhesive formulation of propranolol tablets