One Factor at a Time and factorial experimental design for formulation of l-carnitine microcapsules to improve its manufacturability.

l-carnitine is an essential dietary supplement of physiological importance. Handling and manufacture of l-carnitine is difficult due to its hygroscopic nature, resulting in impairing its flow properties, as well as solid dosage form stability. The study aimed at reducing l-carnitine hygroscopicity through its encapsulation within a hydrophobic, pH-insensitive polymer. A solid in oil in oil (s/o/o) emulsion solvent evaporation technique for microencapsulation was adopted to exclude the possibility of water uptake. The polymers used were two ethyl cellulose (EC) grades with different viscosities. The chosen solvent for the polymer was acetone, and liquid paraffin was the dispersion medium in which both the drug and polymer were insoluble. Sixteen formulations were developed, and evaluated to study the formulation parameters as anti-coalescent type, mixing speed, surfactant type and polymer ratio, and viscosity grade. A "One Factor at A Time" (OFAT) design of experiment, and a factorial design were utilized. Study results revealed that successful microencapsulation occurred by using Aerosil 200 (0.1 %) as anti-coalescent, a mixing speed of 1000 rpm, and Ethocel Std 20 at a 3:1 drug-to-polymer ratio. Microcapsule formulation containing l-carnitine base, successfully compressed into tablets, showed acceptable water content, disintegration time, hardness, and dissolution. Moreover, it showed acceptable stability upon storage at 40 °C at 75 % RH for six months compared to l-carnitine tablets prepared by wet granulation.

Pharmaceutical and medical aspects of hyaluronic acid-ketorolac combination therapy in osteoarthritis treatment: radiographic imaging and bone mineral density.

The objective of this study was to formulate novel painless combined hyaluronic acid (HA)-ketorolac (KT) membrane for the management of osteoarthritis with rapid analgesic onset, thus avoiding HA frequent invasive intra-articular injections and KT gastrointestinal complaints associated with all non-steroidal anti-inflammatory drugs. HA was chemically crosslinked with carbodiimide/glutaraldehyde to yield membrane of low water content. Different in vitro aspects (mechanical properties, water content and in vitro release) were studied leading to an optimized soft, flexible K8 HA membrane containing 30 mg KT that achieved the desired balance of excellent elasticity and low water content. Moreover, a successful retardation of KT release rate was achieved (82%) after 48 h with favored initial fast drug release in the first hour (32.7%) to attain rapid analgesic effect. The clinical assessments in arthritic rats revealed apparent improvement in joint space narrowing, highest increase in bone mineral density at the proximal tibia and distal femur joints with the absence of osteophytosis only in animal group treated with combined HA-KT membrane. Application of K8 membrane was able to preserve KT plasma concentration above its minimum effective concentration for 48 h therefore, would able to replace six commercial tablets each of 10 mg KT.

Miconazole nitrate oral disintegrating tablets: in vivo performance and stability study.

The interest in and need for formulating miconazole nitrate (MN), a broad-spectrum antifungal, as an oral disintegrating tablet for treatment of some forms of candidiasis have increased. Formulation of MN in this dosage form will be more advantageous, producing dual effect: local in the buccal cavity and systemic with rapid absorption. Four formulations were prepared utilizing the foam granulation technique. The prepared tablets were characterized by measuring the weight uniformity, thickness, tensile strength, friability, and drug content. In addition, tablet disintegration time, in vitro dissolution, and in vivo disintegration time were also evaluated. Stability testing for the prepared tablets under stress and accelerated conditions in two different packs were investigated. Each pack was incubated at two different elevated temperature and relative humidity (RH), namely 40 ± 2°C/75 ± 5% RH and 50 ± 2°C/75 ± 5% RH. The purpose of the study is to monitor any degradation reactions which will help to predict the shelf life of the product under the defined storage conditions. Finally, in vivo study was performed on the most stable formula to determine its pharmacokinetic parameters. The results revealed that all the prepared tablets showed acceptable tablet characteristics and were stable under the tested conditions. The most stable formula was that containing magnesium stearate as lubricant, hydrophobic Aerosil R972 as glidant, low urea content, mannitol/microcrystalline cellulose ratio 2:1, and 9% Plasdone XL100 as superdisintegrant. The in vivo results revealed that the tested formula showed rapid absorption compared to the physical blend (t (max) were 1 and 4 h, respectively), while the extent of absorption was almost the same.

Formulation and stability testing of itraconazole crystalline nanoparticles.

Itraconazole (ITZ) crystalline nanoparticles were prepared using relatively simple, low-cost sonoprecipitation technique, in which both the solvent and antisolvent were organic in nature. The effect of stabilizer type (hydroxypropyl methylcellulose, hydroxypropyl cellulose, Inutec SP1®, and pluronic F127), drying method (oven and freeze drying) and matrix former used (Avicel PH101, and Aerosil®200) on the dissolution performance as a key characteristic of nanocrystals was evaluated. In 10 min, all of the prepared nanocrystals showed 3.77-8.59 times improvement in percent drug dissolved compared to pure ITZ. Concerning the effect of stabilizer type, the following rank order can be given: pluronic F127 ≥ hydroxypropyl cellulose ≥ hydroxypropyl methylcellulose (HPMC) > inutec SP1. Freeze-dried ITZ nanocrystals containing Avicel PH 101 showed better dissolution rate compared to other nanocrystals. The chemical structure of itraconazole nanocrystals was not changed as revealed by Fourier transform infrared. Stability study of selected nanocrystals (F5, F7, and F8) revealed physical and chemical stability of F7 and F8, while a decrease in dissolution rate of F5 was observed (although being chemically stable) when stored under high relative humidity conditions. Although inutec is less potent than pluronic F127 and HPMC regarding their effect on dissolution rate enhancement, it is equipotent to pluronic F127 in preserving the rapid drug dissolution.

Formulation of a novel oxybenzone-loaded nanostructured lipid carriers (NLCs).

The objective of the current study was to formulate oxybenzone into nanostructured lipid carriers (NLCs) to enhance its sunscreening efficacy and safety. NLCs of oxybenzone were prepared by the solvent diffusion method. A complete 2(3) factorial design was used for the evaluation of the prepared oxybenzone NLCs. The study design involves the investigation of the effect of three independent variables namely liquid lipid type (Miglyol 812 and oleic acid), liquid lipid concentration (15% and 30%), and oxybenzone concentration (5% and 10% with respect to total lipids) on the particle size (p.s.) , the entrapment efficiency (EE%) and the in vitro drug release after 8 h. The prepared NLCs were spherical in overall shape and were below 0.8 microm. Miglyol 812 and 30% liquid lipid were found to significantly decrease the p.s. and increase the EE% when compared to oleic acid and 15% liquid lipid. Increasing oxybenzone concentration increased significantly the p.s. but did not affect the EE%. NLCs prepared using Miglyol 812, 15% liquid lipid, and 10% oxybenzone showed slower drug release when compared to those prepared using oleic acid, 30% liquid lipid, and 5% oxybenzone, respectively. The candidate oxybenzone-loaded NLC dispersion was then formulated into gel. The incorporation of oxybenzone into NLCs greatly increased the in vitro sun protection factor and erythemal UVA protection factor of oxybenzone more than six- and eightfold, respectively, while providing the advantage of overcoming side effects of free oxybenzone as evidenced by very low irritation potential.

Preparation and evaluation of microemulsion systems containing salicylic acid.

Microemulsions (MEs) are clear, thermodynamically stable systems. They were used to solubilize drugs and to improve topical drug availability. Salicylic acid (SA) is a keratolytic agent used in topical products with antimicrobial actions. The objective of this work was to prepare and evaluate SA ME systems. Different concentrations of SA were incorporated in an ME base composed of isopropyl myristate, water, and Tween 80: propylene glycol in the ratio of 15:1. Three ME systems were prepared: S2%, S5%, and S10% which contain 2%, 5%, and 10% of SA, respectively. Evaluation by examination under cross-polarizing microscope, measuring of percent transmittance, pH measurement, determination of the specific gravity, assessment of rheological properties, and accelerated stability study were carried out. The data showed that the addition of SA markedly affected the physical properties of the base. All systems were not affected by accelerated stability tests. Stability study for 6 months under ambient conditions was carried out for S10%. No remarkable changes were recorded except a decrease in the viscosity value after 1 month. The results suggested that ME could be a suitable vehicle for topical application of different concentrations of SA.

Chitosan based nanocarriers for indomethacin ocular delivery.

Two different chitosan (CS) nanocarriers namely nanoparticles and nanoemulsion were developed to prolong Indomethacin (IM) precorneal residence time and to improve its ocular bioavailability the main limitations in its management of post-operative inflammation and intraocular irritation after cataract extraction. CS-nanoparticles were developed by modified ionic gelation of CS with tripolyphosphate while nanoemulsion was prepared by spontaneous emulsification technique. Transmission electron microscopy revealed regular well-identified spherical shape. The nanoparticles had a mean size of 280 nm, a zeta potential of + 17 mV and high loading efficiency of 84.8 % while the mean size of nanoemulsion was affected by the nature of the surfactant used and varies between 220-690 nm. In vitro release studies, performed under sink conditions, revealed small initial burst release during the first hour followed by slow gradual drug release of 76 and 86% from nanoparticles and nanoemulsion respectively during a 24 h period. In vivo studies and histopathological examination revealed that eyes of rabbits treated with nanoemulsion showed clearer healing of corneal chemical ulcer with moderate effective inhibition of polymorph nuclear leukocytic infiltration (PMNLs) compared with nanoparticles preparation. Moreover, following topical instillation of CS-nanoemulsion to rabbits, it was possible to achieve therapeutic concentration of IM in the cornea through out the duration of the study and fairly high IM level in inner ocular structure, aqueous humor. These levels were significantly higher than those obtained following instillation of IM solution. Therefore, CS nanocarriers developed in this study were able to contact intimately with the cornea providing slow gradual IM release with long-term drug level thereby increasing delivery to both external and internal ocular tissues.