EFFECT OF OILS, SURFACTANTS AND COSURFACTANTS ON PHASE BEHAVIOR AND PHYSICOCHEMICAL PROPERTIES OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS) FOR IRBESARTAN AND OLMESARTAN

Objective: The main purpose of this study was to optimize the different conditions for the preparation of self-nanoemulsifying drug delivery system (SNEDDS) for both Irbesartan (IRB) and Olmesartan (OLM). Methods: Based on solubility study and emulsification efficiency, Preliminary investigations of various oils, surfactants and cosurfactants were carried out for selection of the proper SNEDDS ingredients. Pseudoternary phase diagrams were then plotted using series of concentrations to obtain optimum SNEDDS components that identify the efficient self-nanoemulsifying region. Sixteen unloaded SNEEDS formulae were prepared using Capryol 90, Cremophor RH 40 and Transcutol HP as oil, surfactant and cosurfactant respectively. The prepared SNEDDS were evaluated for self-nanoemulsification time, the effect of dilution (with different volumes at different pH values), optical clarity, viscosity, droplet size analysis as well as the polydispersity index (PDI). SNEDDS formulae were also evaluated for thermodynamic stability and zeta potential to confirm the stability of the prepared SNEDDS. Results: The results showed that the mean droplet size of all reconstituted SNEDDS was found to be in the nanometric range (<100 nm) and showed optimum PDI values. All formulae also showed rapid emulsification time, good optical clarity and found to be highly stable. Formulae with the smallest particle size, lowest emulsification time, best optical clarity and robust to dilution and pH change were selected to be loaded with IRB and OLM for further study. Conclusion: It was concluded that the prepared self-emulsified prototype was ready to incorporate many poorly soluble drugs in order to improve their solubility as well as bioavailability profile. Keywords: Irbesartan, Olmesartan, Self-nanoemulsifying drug delivery system (SNEDDS), Capryol 90, Cremophor RH 40 and Transcutol HP

EFFECT OF ADDITIVES ON IN-VITRO RELEASE OF ORODISPERSIBLE DOSAGE FORM

Objective: The aim of this investigation was to prepare orodispersible tablets of meloxicam using various concentrations of superdisintegrants like Ac-DI-Sol, crospovidone, sodium starch glycolate by the direct compression method. Methods: Nine formulae of Meloxicam orodispersible tablets were prepared. These tablets were evaluated for their drug content, weight variation, friability, hardness, wetting time, In-vitro disintegration time and drug release.Results: All the formulation exhibited hardness between 4.21–4.55 kg/cm2. The tablets were disintegrating within 8.3 to 21.9 sec. Dissolution studies revealed that formula containing 7.5 % sodium starch glycolate showed 100% of drug release, at the end of six minutes. Among the formulated tablets, formula F9 containing 7.5 % sodium starch glycolate showed superior organoleptic properties along with excellent In-vitro disintegration time and drug release as compared to other formulae. The concentration of superdisintegrants had an effect on disintegration time and In-vitro drug dissolution whereas hardness and friability of resulting tablets were found to be independent of disintegrant concentration. It was concluded that the superdisintegrants addition technique is a useful method for preparing orodispersible tablets by the direct compression method.Â

INFLUENCE OF FORMULATION FACTORS ON THE SIZE OF NANOSTRUCTURED LIPID CARRIERS AND NANOEMULSIONS PREPARED BY HIGH SHEAR HOMOGENIZATION

Objective: The main purpose of this work was to elucidate the effect of certain formulation factors on the size of nanostructured lipid carriers (NLCs) and nanoemulsions (NEs) by using high shear homogenization method.Methods: NLCs and NEs were prepared by high shear homogenization method using different liquid lipids types such as (Dermarol DCO® and Dermarol CCT®) at different concentrations. The effect of different concentration ratios of Tween 80 to Span 20 (2.5/1, 5/1, 10/1, 15/1) w/w % and different homogenization speeds (12 000, 18 000 rpm) on the resulted particle size were also studied.Results: The results revealed that the optimum NLCs and NEs resulted when we use Dermarol CCT® with a concentration of 90 % as liquid lipid and decreasing surfactant ratio to (2.5/1) w/w % with increasing the homogenization speed to 18 000 rpm. Conclusion: NLCs and NEs were successfully prepared, and from this study, it can be concluded that NLCs have the optimum particle size than Nanoemulsions

Role of fetal pulmonary artery Doppler in prediction of neonatal respiratory distress in neonates of diabetic mothers

Background: Newborn respiratory complication is one of the most prevalent and life-threatening disorders. The clinical indications of early newborn respiratory distress with consistent radiologic features. The Doppler examination of the primary pulmonary artery in the foetus has been proven to be beneficial. The foetal pulmonary artery At/Et ratio is linked to foetal gestational age and amniotic fluid foetal lung maturity (FLM) tests. The aim of the study was to assess the accuracy of foetal main pulmonary artery (MPA) Doppler indices in prediction of the development of neonatal respiratory distress syndrome (RDS) in diabetic mothers.Methods: This was a prospective observational study carried out on 100 cases of diabetic mothers in obstetrics and gynecology department, Tanta University during one year from the approval of the university counsel. The physician evaluated the foetal heart in a methodical manner after a regular ultrasound assessment that included foetal biometry, anomaly scan, measured foetal weight, and amniotic fluid index. Classic chest radiological features include reticulogranular patterns, air bronchogram and ground glass look, as well as the need for surfactant.Results: PI and RI were significantly higher in newborns with RDS than those without RDS (p=0.025 and 0.036 respectively) PSV and At/Et ratio were significantly reduced in neonates with RDS compared with RDS free ones (p=0.004 and <0.001 respectively). RI was significantly higher in neonates with RDS than those without RDS (P = 0.048) PSV and At/Et ratio were significantly reduced in newborns with RDS compared to RDS free ones (p=0.008 and <0.001 respectively). The ROC curve displayed that the cut off value of ≤0.25 for At/Et ratio was associated with a sensitivity of 76.92%, a specificity of 100.0%, a PPV of 100.0% and a NPV of 96.7% for prediction of neonatal RDS with AUC of 0.925 and p≤0.001.Conclusions: development of neonatal RDS in foetus of diabetic mothers with a cut off value of ≤0.25, a sensitivity of 76.92%, a specificity of 100.0%, a PPV of 100.0%, a NPV of 96.7% and AUC of 0.925 The usage of corticosteroids improved the Doppler indices of main pulmonary artery and is accompanied by less morbimortality related to RDS

Well as its Microcapsules in Rats

ABSTRACT Ketorolac is a potent non-steroidal analgesic drug. It is 36 times more potent than phenyl butazone, and twice as that of indomethacin. The oral administration of ketorolac is associated with high risk of adverse effects such as irritation, ulceration, bleeding of gastrointestinal tract, edema as well as peptic ulceration. These attributes make ketorolac a good candidate for controlled release dosage forms, so as to ensure slow release of the drug in the stomach. The present study reports on the formulation of ketorolac loaded Eudragit RS100, Eudragit RL100 as well as Ethyl cellulose as a controlled release drug delivery system. Solid dispersion and microencapsulation by air suspension method were the techniques of choice in order to coat the drug so as to improve bioavailability and stability and also target a drug at specific sites. The ratio of (1:3) drug to polymer from all polymers used was selected from solid dispersions systems as well as microcapsules to conduct further in vivo evaluation, since it was the best ratio which achieved significant reduction in the release of ketorolac at acidic pH of the stomach and maximal release at alkaline pH of the intestine. The effects of various formulations on ulcer index as well as ulcer incidence were studied. The obtained results indicate that microencapsulation technique was able to protect the stomach from ulcerogenic effect ketorolac compared to solid dispersion technique

EFFECT OF VISCOSITY, SURFACTANT TYPE AND CONCENTRATION ON PHYSICOCHEMICAL PROPERTIES OF SOLID LIPID NANOPARTICLES

Objective: The aim of the current work was to look into the feasibility of planning of solid lipid nanoparticles of Glyceryl mono stearate containing Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide as model drugs.Methods: Solid lipid nanoparticles loaded with three model lipophilic drugs were developed by high shear hot homogenization method. The model drugs used are Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide. Glyceryl monostearate was used as the lipid core; Tween 20 and Tween 80 were employed as surfactants and lecithin asco-surfactant. Many formulation parameters were manipulated to receive high quality nanoparticles. The prepared solid lipid nanoparticles were evaluated by different standardphysical and imaging methods. The efficiency of drug release form prepared formulaewas studied using In vitro technique to utilize of dialysis bag technique. The stability of prepared formulae was studied by thermal procedures and infrared spectrum analysis.The physicochemical properties of the prepared formulae like particle size, drug entrapment efficiency, drug loading capacity, yield content and In vitro drug release behavior were too assessed.Results: The average particle diameter measured by a laser diffraction technique was (194.6±5.03 to 406.6±15.2 NM) for Dibenzoyl peroxide loaded solid lipid nanoparticles, (220±6.2 to 328.34±2.5) NM for Erythromycin loaded solid lipid nanoparticles and (227.3±2.5 to 480.6±24) NM for Triamcinolone acetonide loaded solid lipid nanoparticles. The entrapment efficiency and drug loading capacity, determined with ultravioletspectroscopy, were 80.5±9.45% and 0.805±0.093%, for Dibenzoyl peroxide, 96±11.5 and0.96±0.012 for Triamcinolone acetonide and 94.6±14.9 and 0.946±0.012 for Erythromycinbase respectively. It was found that model drugs showed significant faster release patterns when compared with commercially available formulations and pure drugs(pË‚0. 05). Thermal analysis of prepared solid lipid nanoparticles gave indication ofsolubilization of drugs within a lipid matrix. Fourier Transform Infrared Spectroscopy(FTIR) showed the absence of new bands for loaded solid lipid nanoparticles indicating nointeraction between drugs and lipid matrix and being only dissolved in it. Electronmicroscope of scanning and transmission techniques indicated sphere form of preparedsolid lipid nanoparticles with smooth surface with size below 100 nm.Conclusion: In conclusion, it may be concluded that solid lipid nanoparticles with small particle size have high encapsulation efficiency, and relatively high loading capacity for Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide as model drugs can be obtained by this method.Â

Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation

The main purpose of this study was to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Olmesartan (OLM) for enhancement of its solubility and dissolution rate. In this study, liquid SNEDDS containing Olmesartan was formulated and further developed into a solid form by the spray drying technique using Aerosil 200 as a solid carrier. Based on the preliminary screening of different unloaded SNEDDS formulae, eight formulae of OLM loaded SNEEDS were prepared using Capryol 90, Cremophor RH40 and Transcutol HP as oil, surfactant and cosurfactant, respectively. Results showed that the mean droplet size of all reconstituted SNEDDS was found to be in the nanometric range (14.91–22.97 nm) with optimum PDI values (0.036–0.241). All formulae also showed rapid emulsification time (15.46 ± 1.34–24.17 ± 1.47 s), good optical clarity (98.33% ± 0.16%–99.87% ± 0.31%) and high drug loading efficiency (96.41% ± 1.20%–99.65% ± 1.11%). TEM analysis revealed the formation of spherical and homogeneous droplets with a size smaller than 50 nm. In vitro release of OLM from SNEDDS formulae showed that more than 90% of OLM released in approximately 90 min. Optimized SNEDDS formulae were selected to be developed into S-SNEDDS using the spray drying technique. The prepared S-SNEDDS formulae were evaluated for flow properties, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), reconstitution properties, drug content and in vitro dissolution study. It was found that S-SNEDDS formulae showed good flow properties and high drug content. Reconstitution properties of S-SNEDDS showed spontaneous self-nanoemulsification and no sign of phase separation. DSC thermograms revealed that OLM was in solubilized form and FTIR supported these findings. SEM photographs showed smooth uniform surface of S-SNEDDS with less aggregation. Results of the in vitro drug release showed that there was great enhancement in the dissolution rate of OLM. To clarify the possible improvement in pharmacokinetic behavior of OLM S-SNEDDS, plasma concentration-time curve profiles of OLM after the oral administration of optimized S-SNEDDS formula (F3) were compared to marketed product and pure drug in suspension. At all time points, it was observed that OLM plasma concentrations in rats treated with S-SNEDDS were significantly higher than those treated with the drug in suspension and marketed product

EFFECT OF ADDITIVES ON INTRANASAL PREPARATION OF CYANOCOBALAMIN

The following study involves formulation and evaluation of intranasal preparation of cyanocobalamin. The design of the formula was achieved by preformulation studies of each of solubility, partition, permeation and stability of cyanocobalamin. HPLC (stability indicating assay) wasused only in the stability studies of cyanocobalamin, other parameters were analyzed using a prevalidated spectrophotometric analytical method. In the meantime,such selected adjuncts should have no significant effects on the physical characteristics of the intranasal drops. All components included in the formula were tested regarding their effects on the tested parameter. Also, they were investigated regarding their effect on each parameter tested including the permeation pattern. The latter parameter could be a substitute for in vivo bioavailability, since the data proved that such parameter is highly indicative. Based on the above studies a formula of intranasal drops of cyanocobalamin was designed to contain ingredients suitable for nasal administration. Such formula achieve another important goal which is improving the patient compliance. The formula contains: Cyanocobalamin 0.5%, Sodium metabisulphite 0.5%, β-cyclodextrin 0.5%, Glycerol 10% and Benzalkonium chloride 0.1%. All ingredients were dissolved in a solution prepared at pH value 5.6 using citrate/phosphate buffer.Â

Formulation and in-vitro evaluation of pantoprazole loaded pH-sensitive polymeric nanoparticles

The pH-sensitive polymeric nanoparticles are very efficient delivery systems for acid labile drugs. The main aim of the study was to formulate pantoprazole loaded pH-sensitive polymeric nanoparticles using pH-sensitive polymers to prevent degradation of acid labile drug and evaluate the effect of formation conditions on both nanoparticles characteristics and drug release patterns. Pantoprazole loaded nanoparticles were prepared using nanopercipitation method using pH-sensitive polymers Eudragit S100 or HPMC phthalate HP55. Nanoparticles were characterized for their micromeritic and crystallographic properties, drug content, in-vitro release and the ability to delay pantoprazole release in acidic medium to prevent its degradation. Physicochemical properties of nanoparticles, including particle size, loading capacity (LC), encapsulation efficiency (EE) and in-vitro drug release were significantly affected by formulation conditions. All formulas showed sub micronized size ranging from 299.3 ± 4.62 to 639.7 ± 9.71 nm and achieved delayed release to protect pantoprazole from degradation with different degrees, but generally Hydroxypropyl methyl cellulose phthalate HP55 loaded nanoparticles showed slower drug release than that of Eudragit S100 loaded nanoparticles. Release kinetics and morphological properties of nanoparticles with most delayed release pattern were investigated by Transmission Electron Microscope (TEM) and Compatibility between pantoprazole and polymer was proved by Fourier Transmission Infra Red (FT-IR) and Differential Scanning calorimetry (DSC). The formula stability was evaluated by measuring zeta potential value. Our results suggested that nanoprecipitation method is effective to produce pH-sensitive polymeric nanoparticles, which can be used as a delivery system for acid labile drug (Pantoprazole) to avoid its degradation in acidic medium of the stomach

Effect of Antiadherents on the Physical and Drug Release Properties of Acrylic Polymeric Films

Antiadherents are used to decrease tackiness of a polymer coating during both processing and subsequent storage. Despite being a common excipient in coating formulae, antiadherents may affect mechanical properties of the coating film as well as drug release from film-coated tablets, but how could addition of antiadherents affect these properties and to what extent and is there a relation between the physical characteristics of the tablet coat and the drug release mechanisms? The aim of this study was to evaluate physical characteristics of films containing different amounts of the antiadherents talc, glyceryl monostearate, and PlasACRYL(TM) T20. Eudragit RL30D and Eudragit RS30D as sustained release polymers and Eudragit FS30D as a delayed release material were used. Polymer films were characterized by tensile testing, differential scanning calorimetry (DSC), microscopic examination, and water content as calculated from loss on drying. The effect of antiadherents on in vitro drug release for the model acetylsalicylic acid tablets coated with Eudragit FS30D was also determined. Increasing talc concentration was found to decrease the ability of the polymer films to resist mechanical stress. In contrast, glyceryl monostearate (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher than 25% caused negative effects, which make 25% concentration recommended to be used with acrylic polymers. All antiadherents delayed the drug release at all coating levels; hence, different tailoring of drug release may be achieved by adjusting antiadherent concentration with coating level