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.

The Potential of a Site-Specific Delivery of Thiamine Hydrochloride as a Novel Insect Repellent Exerting Long-Term Protection on Human Skin: In-vitro, Ex-vivo Study and Clinical Assessment.

Thiamine hydrochloride (TH) was thought to exert a good insect repellent activity. The purpose of this work was to develop a formulation that releases TH in sustained regimen on human skin. Long lasting protection against mosquito bites was achieved. Pullulan acetate (PA) was used to prepare TH nanospheres. Optimal system was incorporated in Pluronic® hydrogel. Formulae were tested for in-vitro release and ex-vivo permeation. Complete protection time (CPT) was done adopting Kaplan-Meier survival function for the synthetic repellent (DEET), TH solution and nanospheres in hydrogel. Release profile of TH solution, nanospheres and nanosphere-loaded hydrogel (DG) demonstrated an added effect of DG, where t 1/2 was 11.2 ± 1.4 h. SEM for DG showed homogenous dispersion of nanospheres inside the matrix of the gel. Ex-vivo permeation showed only 0.761 ± 0.04% of TH in hydrogel permeated the skin after 12 h, while 44.98 ± 3.2% permeated when TH solution was applied. Clinical study revealed a significant difference in CPT between TH solution with either DEET or (DG) (p<0.05), and no significant difference between DEET and DG with CPT 400 ± 31 and 360 ± 18 min, respectively (P > 0.05). The high efficacy of TH-loaded hydrogel rendered it a successful alternative for DEET, offering long protection against mosquito bites.

Effectuation of loading a natural acetyl carnosine derivative within a promising cross-linked cyclodextrin spongey-like nanospheres on Physicochemical characterization and release behavior.

This study centered on the ability of the cross-linked nano-sponge system to load the drug and to improve its physicochemical and dissolution properties. A spectrophotometric method was used to determine the wavelength of maximum absorbance of the drug. The ultrasonic-assisted synthesis method was used for nano-sponge preparation. Solution-state interactions, encapsulation efficiency and production yield, and in-vitro release were also investigated. Nano-sponges were characterized by Transmission Electron-Microscopy (TEM), Scanning Electron-Microscopy (SEM), Fourier Transform-Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and X-Ray Diffractometry (X-RD) studies. The maximum absorption wavelength of N-acetyl-L-carnosine was found to be at 210 nm. Solution-state interaction studies revealed a bathochromic shift. The production yield of nano-sponges ranged from 59.58% to 72.54%. In-vitro release study showed a sustained drug release for 228 hours. TEM images showed regular spherical shapes and sizes of nano-sponges. Their average particle size ranged from 28 nm to 79.2 nm. DSC data documented the drug-polymer interactions. FT-IR determined the presence of functional groups. X-RD showed the physicochemical characteristics of nano-sponges. Proving successful development of N-acetyl-L-carnosine polymeric nano-sponge system with a suitable drug delivery over an extended period beside a noticeable improvement in the physicochemical characterization.

Pediatric Coping During Venipuncture With Virtual Reality: Pilot Randomized Controlled Trial.

BACKGROUND: Virtual reality (VR) has shown promise in reducing children's pain and anxiety during venipuncture, but studies on VR lack objective observations of pediatric coping. Notably, the process of capturing objective behavioral coping data can be labor- and personnel-intensive. OBJECTIVE: The primary aims of this pilot trial were to assess the feasibility of conducting a trial of VR in a pediatric emergency department and the feasibility of documenting observed coping behaviors during pediatric procedures. Secondarily, this study examined whether VR affects child and caregiver coping and distress during venipuncture in the pediatric emergency department. METHODS: This stratified, randomized, controlled pilot trial compared coping and distress between child life-supported VR engagement and child life specialist support without VR during painful procedures in children aged 7-22 years in the pediatric emergency department. An external control (reference group) received no standardized support. Primary feasibility outcomes included rates of recruitment, rates of withdrawal from VR, and rates of completed Child Adult Medical Procedure Interaction Scale-Short Form (CAMPIS-SF) observations. Secondary clinical outcomes were applied to venipuncture procedures and included CAMPIS-SF coping and distress (range 0-1.0), pain and anxiety on a visual analog scale (range 0-10), and cybersickness symptoms. RESULTS: Overall recruitment was 93% (66/71), VR withdrawal rate was 27% (4/15), and of the completed procedures, 100% (63/63) CAMPIS-SF observations were completed. A total of 55 patients undergoing venipuncture in the pediatric emergency department were included in the analyses of clinical outcomes: 15 patients (15 caregivers) randomized to VR, 20 patients (15 caregivers) randomized to child life specialist support, and 20 patients (17 caregivers) in the reference group. Patient coping differed across groups with higher coping in the VR group and child life specialist group than in the reference group (P=.046). There were no significant differences in the distress and pain ratings for patients and caregivers between the groups. Caregivers rated the lowest perceived anxiety in the child life specialist group (P=.03). There was no apparent change in cybersickness symptoms before and after VR use (P=.37). CONCLUSIONS: Real-time documentation of observed behaviors in patients and caregivers was feasible during medical procedures in which VR was utilized, particularly with the availability of research staff. VR and child life specialists improved coping in children during venipuncture procedures. Given the high participation rate, future studies to evaluate the efficacy of VR are recommended to determine whether an off-the-shelf VR headset can be a low-cost and low-risk tool to improve children's coping during venipuncture or other related procedures. TRIAL REGISTRATION: ClinicalTrials.gov NCT03686176; https://clinicaltrials.gov/ct2/show/NCT03686176.

Resource Use During Pediatric Venipuncture With Virtual Reality: Secondary Analysis of a Randomized Controlled Pilot Trial.

OBJECTIVES: Virtual reality (VR) therapy is growing in use and popularity during pediatric medical procedures. Currently, data that describe the hospital resources used during pediatric procedures with off-the-shelf VR games that are not tailored to medical procedures are lacking. In this study, we aimed to characterize procedural resources associated with VR use during venipuncture in a pediatric emergency department. METHODS: This was a secondary analysis of a 2-arm randomized, controlled pilot trial with an external group. Resource use was evaluated in 3 groups: child life (CL)-supported VR engagement, CL support without VR, and a reference group that received no intervention (ie, no CL and no VR). RESULTS: The study sample (N = 55) included the following: 15 patients randomly assigned to VR, 20 patients randomly assigned to CL, and 20 patients in the reference group. There was a significant difference in procedure duration, with the VR group exhibiting the longest duration compared with the CL and reference groups (P = .01). CONCLUSIONS: Longer procedure times associated with VR use during venipunctures (4-6 minutes on average) may be attributed to pauses to troubleshoot VR games not tailored for medical procedures. Although they are inexpensive and accessible, nontailored VR games may warrant the need for dedicated staff to provide restraint and/or assistance to navigate the VR application. In this study, we offer a protocol on the application of nontailored VR games for pediatric procedures. For those considering a VR program in an inpatient setting, the benefits of pain/anxiety reduction must be weighed against the resources needed, including device costs, staff availability, and increased procedure duration.

A Pilot Clinical Study on Thiamine Hydrochloride as a New Mosquito Repellent: Determination of the Minimum Effective Dose on Human Skin.

Thiamine hydrochloride has been suggested as a natural, safe yet effective alternative for chemical insect repellents. However, there is a demand for a reassessment of the minimum required dose that is sufficient to perform a topical repellency on the human skin. Therefore, the purpose of the current work is to establish a dose-response curve from which the effective dose (ED) is calculated. A series of increasing concentrations of thiamine hydrochloride were applied to the forearm of adult volunteers, the number of bites was counted and the percent repellency calculated accordingly. Data of percent repellency were converted to probit values which were plotted against log doses. A linear relation was obtained from the dose-response curve with an r2 = 0.958. Statistical validation of the equation was tested through linear regression analysis, where the slope and intercept were found significant from zero. No significant difference was shown between observed and expected responses (p > 0.05). ED 50 and 99.9% were computed from the linear equation and found to be 4.57 and 344 mg, respectively. This finding can be supported by future works in which a proper formulation of thiamine hydrochloride in the respective doses would be presented. One can get prolonged safe protection against insect bites.

Stabilizing excipients for engineered clopidogrel bisulfate procubosome derived in situ cubosomes for enhanced intestinal dissolution: Stability and bioavailability considerations.

Clopidogrel bisulfate (CB) is a golden antiplatelet treatment, yet its benefits are limited by its low bioavailability (<50%) caused by poor intestinal solubility and absorption. The present study aims to improve CB intestinal solubility and absorption through developing a novel stable dry CB procubosomes tablets ready to disintegrate and re-disperse upon dilution in the GIT forming in situ CB cubosome nanoparticles while simultaneously overcome the poor stability of conventional cubosome dispersion at room temperature. Glyceryl monooleate based CB cubosome dispersion was prepared using Poloxamer 407 as surfactant, freeze dried using different stabilizing excipients (dextrose, mannitol and avicel) then compressed into procubosome tablets. The effect of excipient's physicochemical properties on the flowability, in vitro dissolution and stability at accelerated conditions (40 ±â€¯2 °C/75 ±â€¯5% RH) were evaluated. The prepared procubosomes exhibited an excipient type dependent dissolution profile where Avicel based procubosome tablet CF2 showed the highest in vitro dissolution profile among other excipients used during the freeze drying process. Upon transition to intestinal pH of 6.8 to mimic the drug absorption site, CF2 procubosome Avicel tablet, was able to preserve the enhanced CB release profile (99.6 ±â€¯6.92%) compared to commercial Plavix® where, CB dissolved % dropped dramatically to 79.1 ±â€¯2.45%. After storage for six months, CF2 retained the fresh tablet drug content of 98.5 ±â€¯5.82% and dissolution properties. Moreover, following oral administration in rabbits, CF2 showed higher relative bioavailability (153%) compared to commercial Plavix® with significant higher Cmax,shorter tmax, as well as enhanced antiplatelet activity.

Cubosomes as Oral Drug Delivery Systems: A Promising Approach for Enhancing the Release of Clopidogrel Bisulphate in the Intestine.

Clopidogrel bisulphate (CB) is a first line antiplatelet drug for treatment of myocardial infarction and stroke. Yet, its efficacy is limited by its poor solubility in intestinal pH, its main site of absorption. The main aim of this study is to enhance the intestinal release of CB by loading in cubosome nanoparticles. Glyceryl monooleate (GMO) based CB loaded cubosomes were prepared using a 33 factorial design to study the effect of polyvinyl alcohol (PVA), poloxamer 407 (PL407) concentrations and ratio of CB to the disperse phase on the average particle size, entrapment efficiency (%EE), in vitro release at 15 min (%Q15), and their morphology using transmission electron microscopy (TEM). The release of the optimized formula was compared in buffer transition media (pH 1.2 for 2 h then pH 6.8 for 6 h) to free drug to study the effect of the changing pH in the gastrointestinal tract (GIT) on CB release. The antihaemostatic properties of the optimized formula were compared to the commercial product Plavix® using bleeding time (BT) model in rabbits. The prepared cubosomes were in the nano range (115±6.47 to 248±4.63 nm) with high %EE (91.22±4.09% to 98.98±3.21%). The optimized formula showed significantly higher (p<0.05) CB release in intestinal pH and preserved the high% released (95.66±1.87%) in buffer transition release study compared to free drug (66.82±4.12%) as well as significantly (p<0.05) higher antihaemostatic properties with longer BT (628.47±6.12 s) compared to Plavix® (412.43±7.97 s). Thus, cubosomes proved to be a successful platform to enhance the intestinal release of CB and improve its absorption.

Comparative study on the in vitro performance of blister molded and conventional lornoxicam immediate release liquitablets: accelerated stability study and anti-inflammatory and ulcerogenic effects.

CONTEXT: Lornoxicam is a potent non-steroidal anti-inflammatory drug (NSAID). It shows limited solubility in the gastric pH, delayed bioavailability and pharmacodynamic effects with aggravated gastric side effects (due to longer residence in the stomach wall). OBJECTIVE: To enhance dissolution of lornoxicam in the gastric fluid and expectedly absorption and pharmacological action, with less ulcerogenic effects. MATERIALS AND METHODS: Formulation of immediate release (IR) lornoxicam liquitablets containing both liquid and solid release modulators (wetting agent, solubilizers and microenvironmental pH modifiers). Beside the traditional direct compression technique employed for the preparation of liquitablets a new technique, blister molding, was also used. The effect of the two different manufacturing methods on the fast release characteristics (rapid disintegration and dissolution) was studied. Stability and pharmacological activity of the optimum formula were also explored. RESULTS: Similarity factor pointed out the superiority of molding technique in enhancing dissolution of lornoxicam owing to significant crystallinity reduction (XRD). Optimum formula showed negligible change in drug content and dissolution profiles over 12 weeks, significantly improved anti-inflammatory activity and significantly reduced gastric ulcerative effect over pure lornoxicam and commercial formula. DISCUSSION AND CONCLUSION: Blister molded lornoxicam liquitablet of improved dissolution and pharmacological activity and less gastric erosion was successfully prepared.

Tretinoin-loaded liposomal formulations: from lab to comparative clinical study in acne patients.

Topical tretinoin is the most commonly used retinoid for acne. However, its irritative potential on the applied area and the barrier properties of the stratum corneum limit its use. The objective of the present study was to formulate tretinoin liposomal gel to obtain a formula with lower skin irritation potential and greater clinical effect. A statistical 2(4) factorial design was adopted. Sixteen formulae prepared and were properly evaluated. A candidate formula (F13G) prepared with 0.025% tretinoin, phospholipid- cholesterol-dicetylphosphate (9:1:0.01) and incorporated in 1% carbopol gel was selected for skin irritation test. Clinical study was conducted on acne patients and compared to marketed product. All liposomes formulations were spherical in shape. The addition of cholesterol in the film hydration method significantly decreased the vesicle size, and increased the percentage of incorporation efficiency at (p < 0.05). The presence of dicetylphosphate significantly increased drug release but did not affect the percentage of incorporation efficiency and vesicle size. The results of the clinical study in acne patients revealed that F13G showed significantly higher efficacy when compared to marketed product (p < 0.05).

Preclinical evaluation of dual action intranasal formulation intended for postoperative/cancer associated therapies.

Granisetron hydrochloride is a potent antiemetic yet experiencing first pass metabolism. Ketorolac tromethamine is a potent analgesic NSAID that is known to cause gastrointestinal complications. The purpose of this study is to prepare combined in situ nasal copolymer thermal gel combining both drugs for the management of postoperative and cancer associated nausea, vomiting and pain while avoiding the problems associated with their therapy. In situ gelling nasal formulations with/without different mucoadhesive polymers were prepared and evaluated. Viscosity of different formulations was measured and correlated to in-vitro drug release. Selected formulae were evaluated for in-vivo mucociliary transit time. Based on in-vitro release pattern and mucociliary transit time, the selected formula F4 was evaluated for chemical and thermal anti-nociception activity in rats following intranasal or intraperitoneal administration. Only the intra-nasal administration of the selected formulation F4 showed significant analgesia against chemical nociception during both the early and late phases. Also, intranasal administration of the selected formulation F4 showed significant analgesia against thermal nociception. F4 intranasal formulation may offer higher therapeutic value than oral administration as it may not only avoid granisetron first pass metabolism but may also minimize ketorolac gastrointestinal adverse effects as well.

Formulation of tretinoin-loaded topical proniosomes for treatment of acne: in-vitro characterization, skin irritation test and comparative clinical study.

Tretinoin (TRT) is a widely used retinoid for the topical treatment of acne, photo-aged skin, psoriasis and skin cancer which makes it a good candidate for topical formulation. Yet side effects, like redness, swelling, peeling, blistering and, erythema, in addition to its high lipophilicity make this challenging. Therefore, the aim of this study was the development of TRT-loaded proniosomes to improve the drug efficacy and to increase user acceptability and compliance by reducing its side effects. Nine formulae were prepared according to 3(2) factorial design and were evaluated for their morphology, vesicle size, entrapment efficiency (EE %), and% of drug released after 5 h. Hydrogel of the candidate formula, N8G (proniosomes prepared with 0.025% TRT, and Span60: cholesterol molar ratio of 3:1 and incorporated in 1% carbopol gel) was developed and evaluated for skin irritation test and clinical study in acne patients compared to marketed product. Candidate formula showed higher efficacy and very low irritation potential when compared to marketed product in human volunteers.

Provesicular granisetron hydrochloride buccal formulations: in vitro evaluation and preliminary investigation of in vivo performance.

Granisetron hydrochloride (granisetron) is a potent antiemetic that has been proven to be effective in acute and delayed emesis in cancer chemotherapy. Granisetron suffers from reduced oral bioavailability (≈60%) due to hepatic metabolism. In this study the combined advantage of provesicular carriers and buccal drug delivery has been explored aiming to sustain effect and improve bioavailability of granisetron via development of granisetron provesicular buccoadhesive tablets with suitable quality characteristics (hardness, drug content, in vitro release pattern, exvivo bioadhesion and in vivo bioadhesion behavior). Composition of the reconstituted niosomes from different prepared provesicular carriers regarding type of surfactant used and cholesterol concentration significantly affected both entrapment efficiency (%EE) and vesicle size. Span 80 proniosome-derived niosomes exhibited higher encapsulation efficiency and smaller particle size than those derived from span 20. Also, the effect of %EE and bioadhesive polymer type on in vitro drug release and in vivo performance of buccoadhesive tablets was investigated. Based on achievement of required in vitro release pattern (20-30% at 2h, 40-65% at 6h and 80-95% at 12h), in vivo swelling behavior, and in vivo adhesion time (>14 h) granisetron formulation (F19, 1.4 mg) comprising HPMC:carbopol 974P (7:3) and maltodextrin coated with the vesicular precursors span 80 and cholesterol (9:1) was chosen for in vivo study. In vivo pharmacokinetic study revealed higher bioavailability of buccal formulation relative to conventional oral formulation of granisetron (AUC0-∞ is 89.97 and 38.18 ng h/ml for buccal and oral formulation, respectively). A significantly lower and delayed Cmax (12.09±4.47 ng/ml, at 8h) was observed after buccal application compared to conventional oral tablet (31.66±10.15 ng/ml, at 0.5 h). The prepared provesicular buccoadhesive tablet of granisetron (F19) might help bypass hepatic first-pass metabolism and improve bioavailability of granisetron with the possibility of reducing reported daily dose (2mg) and reducing dosing frequency.

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.