Influence Of Formulation Parameters Research Articles

Nose-to-Brain Targeted Delivery of Donepezil Hydrochloride via Novel Hyaluronic Acid-Doped Nanotransfersomes for Alzheimer's Disease Mitigation

Alzheimer's disease is the most serious neurodegenerative disorder characterized by cognitive and memorial defects alongside deterioration in behavioral, thinking and social skills. Donepezil hydrochloride (DPZ) is one of the current two FDA-approved cholinesterase inhibitors used for the management of Alzheimer's disease. The current study aimed to formulate hyaluronic acid-coated transfersomes containing DPZ (DPZ-HA-TFS) for brain delivery through the intranasal pathway to surpass its oral-correlated GIT side effects. DPZ-HA-TFS were produced using a thin film hydration method and optimized with a 24 factorial design. The influence of formulation parameters on vesicle diameter, entrapment, cumulative release after 8 h, and ex vivo nasal diffusion after 24 h was studied. The optimal formulation was then evaluated for morphology, stability, histopathology and in vivo biodistribution studies. The optimized DPZ-HA-TFS formulation elicited an acceptable vesicle size (227.5 nm) with 75.83% entrapment efficiency, 37.94% cumulative release after 8 h, 547.49 µg/cm2 permeated through nasal mucosa after 24 h and adequate stability. Histopathological analysis revealed that the formulated DPZ-HA-TFS was nontoxic and tolerable for intranasal delivery. Intranasally administered DPZ-HA-TFS manifested significantly superior values for drug targeting index (5.08), drug targeting efficiency (508.25%) and direct nose-to-brain transport percentage (80.32%). DPZ-HA-TFS might be deemed as a promising intranasal nano-cargo for DPZ cerebral delivery to tackle Alzheimer's disease safely, steadily and in a non-invasive long-term pattern.

Influence of grease formulation parameters on the tribological property of rice bran oil based lubricating grease

AbstractThe negative environmental impacts and depletion of resources caused due to the excess usage of petroleum based products made researchers to think about an alternative biodegradable product. In the present study, rice bran oil (RBO) was used as a base oil for formulating 16 different grease samples. The thickener used was generated in situ by mixing 12‐hydroxy stearic acid (12 HSA) to calcium hydroxide at a different ratio from 1.25 to 2. The formulation parameters such as weight % of thickener, saponification time, and maximum temperature spanned the ranges 5–11 wt.%, 1–2.5 h, and 150–180°C, respectively. The tribological properties such as wear scar diameter (WSD) and friction of 16 different grease samples formulated by varying these parameters were evaluated using a standard four‐ball tester as per ASTM standards. The grease samples were characterized by evaluating the penetration value using a standard cone penetrometer. The influence of these formulation parameters on the experimentally evaluated properties was also examined in this work. The results indicated that the variation of these parameters during grease formulation has a significant influence on the evaluated properties.

Clarithromycin Loaded Chitosan Nanoparticles: Development and Characterization

Background:: Chitosan nanoparticles have been extensively studied and used due to their well-recognized applicability in various fields. Chitosan, a natural polysaccharide polymer, is extensively used in pharmaceuticals to deliver a wide variety of therapeutic agents. Chitosan is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of multi particles, particularly nano- and microparticles. Objective:: The main aim of the present study was to optimize the conditions for the preparation of chitosan nanoparticles to get optimal particle size, with optimal zeta potential and narrow polydispersity index and anti-bacterial activity. Methods:: Include the ionic gelation technique for chitosan nanoparticle preparation. The influence of formulation parameters and process parameters on the chitosan nanoparticles were investigated. Besides, the suspension stability of the prepared nanoparticles was also assessed on storage at 4°C. Results: The formulation and process parameters showed a significant effect on the physicochemical and morphological characteristics of the chitosan nanoparticles. The chitosan nanoparticles prepared under optimum conditions (chitosan concentration of 0.5% w/v, CS: TPP mass ratio of 1:3, initial pH of chitosan solution of 4.5, stirred at 750 rpm for 30 min) had shown a mean particle size of ~326.8±15 nm, zeta potential of +28.2 ± 0.5 mV, and PDI of 0.21 ± 0.02. The encapsulation of the clarithromycin slightly increased the polydispersity index, but the zeta potential of the unloaded nanoparticles was not affected while the particle size increased. Under optimum conditions, clarithromycin encapsulation efficiency into nanoparticles was found to be 70%. Additionally, chitosan- tripolyphosphate nanoparticles were shown to be stable for a minimum of fifteen days in deionized water at 4°C. Conclusion:: The current study concludes the optimal conditions to formulate the chitosan nanoparticles with optimal physicochemical characteristics.

Influence of formulation parameters on lipid oxidative stability of Pickering emulsion stabilized by hydrophobically modified starch particles

Sunflower oil–in–water Pickering emulsions were fabricated using octenyl succinic anhydride modified rice starches as particulate stabilizers. The major factors influencing oxidative stability of emulsions were investigated. Results indicated that oxidative stability was enhanced with the increase of starch particle concentration and oil fractions. The emulsions had excellent oxidative stability at pH 6.0–7.0. Low NaCl concentration of 40 mmol/L slightly increased lipid stability, while high NaCl concentration decreased oxidative stability. Sucrose concentrations ranging from 0 to 200 mmol/L had no obvious effect on oxidative stability. Results of confocal laser scanning microscope showed that the hydrophobically modified starch particles built up 3D-network barrier around oil droplets at oil–water interface, which increased the viscosity of continuous phase and prevented oil droplets from contacting with pro-oxidants in water phase, thus decreasing peroxide value and thiobarbituric acid reactive substances. These results implied that starch-based Pickering emulsion may be a promising delivery vehicle for bioactive compounds.

Influence of Formulation Parameters on Redispersibility of Naproxen Nanoparticles from Granules Produced in a Fluidized Bed Process.

The particle size reduction of active pharmaceutical ingredients is an efficient method to overcome challenges associated with a poor aqueous solubility. With respect to stability and patient’s convenience, the corresponding nanosuspensions are often further processed to solid dosage forms. In this regard, the influence of several formulation parameters (i.e., type of carrier material, type and amount of additional polymeric drying excipient in the nanosuspension) on the redispersibility of naproxen nanoparticle-loaded granules produced in a fluidized bed process was investigated. The dissolution rate of the carrier material (i.e., sucrose, mannitol, or lactose) was identified as a relevant material property, with higher dissolution rates (sucrose > mannitol > lactose) resulting in better redispersibility of the products. Additionally, the redispersibility of the product granules was observed to improve with increasing amounts of polymeric drying excipient in the nanosuspension. The redispersibility was observed to qualitatively correlate with the degree of nanoparticle embedding on the surface of the corresponding granules. This embedding was assumed to be either caused by a partial dissolution and subsequent resolidification of the carrier surface dependent on the dissolution rate of the carrier material or by resolidification of the dissolved polymeric drying excipient upon drying. As the correlation between the redispersibility and the morphology of the corresponding granules was observed for all investigated formulation parameters, it may be assumed that the redispersibility of the nanoparticles is determined by their distance in the dried state.

Influence of formulation parameters on the freeform extrusion process of ceramic pastes and resulting product properties

The rheology of a ceramic paste is known to be a key factor in the process of additive manufacturing of ceramic parts via extrusion freeforming. The rheological properties of ceramic pastes can be influenced by several formulation parameters. In this study, the mutual influence between formulation parameters, printing properties and mechanical properties of ceramic pastes (Al2O3) and the resulting green bodies are investigated. Special focus is set on elucidating the origins and causes of the altered paste properties to allow targeted material development of pastes for the use in extrusion freeforming. Glycerine and nanoparticulate boehmite needles are tested as additives and they successfully improve the printability in the extrusion freeforming process of the paste and compression strength of the green body. Considerable difference in the dependency of the mechanical properties on the formulation parameters was detected after a partial sintering of the green bodies at 1000 °C. Dewatering, shrinkage during drying and a running of the deposited lines could be reduced successfully by adjusting the formulation. The impact of the formulation parameters on the printing performance could be linked to the dependency of the volume flow rate on the ratio of pressure over viscosity.

Development of a Cassava Starch-Based Foam Incorporated with Grape Stalks Using an Experimental Design

Concern about pollution caused by the incorrect disposal of plastic materials has led to an increasing interest in packaging made from natural resources and biodegradable materials. In this context, cassava starch-based foams incorporated with Cabernet Sauvignon grape stalks, one of the main residues from the wine industry, were prepared by thermal expansion, a simple and fast process. Grape stalks in small granulometries can provide a homogeneous matrix and help improve foam resistance. Glycerol, a by-product of the biodiesel production process, was added to improve the batter processability and the flexibility of the foams. Therefore, the influence of formulation parameters, such as the percentage of glycerol and grape stalks addition, and the particle size of the stalks was studied using a central composite experimental design. The desirability function of Statistica software was used to obtain a formulation that presented better properties for the foams. Results showed that the formulation with 13.6 wt% glycerol, 18.4 wt% grape stalks in the smallest particle size analyzed (O < 0.18 mm) was able to improve mechanical and humidity related properties and density of the foams. These results indicate that the foams developed in this study could be used as a substitute for EPS trays.

Influence of formulation parameters on encapsulation of doxycycline in PLGA microspheres prepared by double emulsion technique for the treatment of periodontitis

Advanced therapeutics often employ controlled release of pharmaceutics by the use of microspheres. However, common techniques to produce microspheres suffer from poor encapsulation efficiency (EE) of hydrophilic drugs. The aim of this study was to assess various formulation parameters to enhance doxycycline (DOX) encapsulation into poly(D, L-lactide-co-glycolide) (PLGA) microspheres prepared by double emulsion (water/oil/water) solvent evaporation technique. The parameters included variations in co-solvents, external aqueous phase (W2) pH, and PLGA end-groups (ester- or acid-terminated). Results showed that the formulated microspheres sized <10 μm and were of low polydispersity. Furthermore, an external phase pH of 9.0 was most suitable for the incorporation of the drug. Additionally, the replacement of the polymer phase with a co-solvent system (1:5, EtOH:DCM %) significantly enhanced the drug EE using acid-terminated PLGA polymer. Drug release kinetics showed an initial burst release phase, followed by a controlled exponential phase that lasted up to 21 days. Furthermore, in vitro studies revealed concentration-dependent toxicity using periodontal ligament cells (PDLCs) and antibacterial properties against periodontal pathogens. Overall, this study demonstrated the optimal formulation parameters needed to achieve a high encapsulation of water-soluble drug into PLGA microspheres using emulsification techniques.

Microencapsulation of caffeic acid and its release using a w/o/w double emulsion method: Assessment of formulation parameters

Caffeic acid (CAF)has numerous health benefits mainly due to its antioxidant, antibacterial and fungicide properties. However, its incorporation in skin care products as anti-aging and the photoprotective agent is still limited due to its solubility and stability in oily matrices or solutions balanced with the skin pH. In this research, CAF–ethyl cellulose (EC) microparticles were produced by water-in-oil-water double emulsion solvent evaporation encapsulation technique using a biocompatible polymer, EC, as a coating material and a surfactant, polyvinyl alcohol, as a stabilizer of the double emulsion. The study assessed the influence of formulation parameters as the solubility of the polymer in organic solvents and the polymer concentration on microparticles final characteristics. CAF–EC microparticles were characterized by product yield, encapsulation efficiency, mean particle size, particle size distribution and polydispersity and imaged by scanning light microscopy. In vitro release profiles were obtained in water and octanol to mimic oily based and water-based matrices balanced with the skin pH. In vitro release kinetics studies were carried out to investigate the release pattern of CAF in simulated cosmetic formulations. Both the product yield and the encapsulation efficiency were found to be dependent on the solubility of the polymer in the organic phase. The product yield was mainly affected by operational factors such as the sticking and the agglomeration of the polymer to the walls and the magnet stirring during microparticles hardening and results from the encapsulation efficiency revealed that an increase of the polymer concentration led to an increase of the encapsulation efficiency. The usage of a water-soluble solvent contributed to a decrease in the mean particle size and reduction of polydispersity with higher polymer concentrations. The polymer concentration, the polymer solubility in the organic phase and the amount of CAF entrapped shown to affect the release in water, whereas the release in octanol was mainly independent of the amount of CAF entrapped in EC microparticles. The double emulsion solvent evaporation technique and the assessment of the selected formulation conditions have given significant and innovative insights on the microencapsulation of bioactive ingredients for cosmetics formulations.

A potential antibacterial wound dressing of cefadroxil chitosan nanoparticles in situ gel: Fabrication, in vitro optimization and in vivo evaluation

Wound healing following skin injury is a natural phenomenon that usually lacks quality, rapidity, and aesthetics. Thus, the purpose of this study was to fabricate a new easily applied in situ gel of cefadroxil (CDX) loaded chitosan nanoparticles (CDX-CSNPs) that could promote wound healing, capable of inhibiting the possible accompanying bacterial infection. The nanoparticles were prepared by double emulsion technique and the influence of formulation parameters on drug entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP) were investigated using a full factorial design. The results show that the optimized CDX-CSNP1 composed of low molecular weight chitosan (0.2%w/v) was spherical with EE%, PS, PDI and ZP of 84.25 ± 0.02, 408.30 ± 53.17 nm, 0.458 ± 0.048 and 22.80 ± 0.57 mV, respectively. DSC and XRD studies confirmed the amorphous nature of the drug. After ensuring the safety and non toxicity of CDX-CSNP1 in situ gel through cytotoxic study, the antibacterial activity was evaluated using a rat skin infection model against Staphylococcus aureus. Compared to the rats treated with free CDX, the CDX-CSNP1 treated group revealed a remarkable accelerated wound healing process and bacterial clearance which was further confirmed by the histopathological examination of skin biopsies.

Influence of formulation parameters on encapsulation and release characteristics of curcumin loaded in chitosan-based drug delivery carriers

Drugs derived from plants with excellent chemotherapeutic effectiveness and relatively low toxicity may fail to scale through the phyto-drug discovery channel due to lack of appropriate drug delivery systems. These phytoceuticals need compatible carriers that will improve their stability, bioavailability and enhance their effectiveness. In this study, chitosan-based drug delivery carriers (DDCs) containing curcumin as phyto-drug model were prepared either via ionotropic gelation with tripolyphosphate or polyelectrolyte complexation with alginate. Influence of formulation parameters was evaluated using encapsulation and release characteristics as response indices. Crosslinking time, pH of chitosan solution and concentration of curcumin, alginate or tripolyphosphate significantly influenced the encapsulation efficiency, rate of curcumin release and mean release time (MRT) in simulated gastric fluid (SGF). Roughly spherical chitosan-based micro-beads with copious pores within the matrix and of improved encapsulation efficiency (82–93%) were prepared using optimized set of formulation parameters. Incorporation of alginate into the chitosan DDC reduced erosion of curcumin by 30% and extended MRT by 180 min in SGF without net delineating change in release profiles of curcumin in simulated physiological saline and intestinal fluids. Time-dependent in vitro study showed that radical scavenging activity ratio of curcumin was enhanced via encapsulation in chitosan-based DDCs.

Preparation and characteristics of multiple emulsions containing liquid crystals

ABSTRACTIn this paper, multiple emulsions containing liquid crystals were prepared successfully and the influence of formulation parameters on the formation mechanism was studied. Moreover, differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS) spectra analysis and stability analysis were used to characterise the property of them. The results showed that the chemical structure of water-in-oil (W/O) emulsifiers directly impacted on the formation of multiple structure, but the effect on the formation of liquid crystal structure was negligible. With the gap of the polarity between inner and outer liquid oils decreased, both multiple structure and liquid crystal structure were harder to form. The content of sodium chloride in internal aqueous phase, which should be neither too high nor too low, has great impact on the formulation of multiple structure. It was easier to form two structures simultaneously when the carbon chain length of fatty alcohols was closer to that of emulsifier C22 alkyl polyglucoside (202). DSC elucidated the phase transitions of water in the liquid crystal layer and the W/O emulsions. SAXS indicated that the liquid crystal orientation was lamellar. The stability analysis showed that the presence of liquid crystal structure had a significant contribution to the stability of the multiple emulsions.

Experimentally designed lyophilized dry emulsion tablets for enhancing the antihyperlipidemic activity of atorvastatin calcium: Preparation, in-vitro evaluation and in-vivo assessment

This article presents the development of lyophilized orally disintegrating tablets prepared with the dry emulsion technique to enhance the in-vitro dissolution and in-vivo performance of the poorly bioavailable drug atorvastatin calcium (ATV). Tablets were fabricated by freeze-drying o/w emulsions of ATV. The Emulsions were prepared using a matrix former solution (alginate or gelatin, 2 or 4%) containing a sugar alcohol (mannitol) and a collapse protectant (glycine) as the water phase and Labrafac® as the oil phase in the presence of surfactant (synperonic® PE/P 84 or synperonic® F108) under proper homogenization. The influence of formulation parameters on friability of the prepared tablets, disintegration time and in-vitro dissolution of the drug from these tablets were investigated. Results showed the significant influence of the matrix former and emulsifier type on the disintegration time. In-vitro dissolution study revealed the enhanced dissolution rate of ATV from the lyophilized dry emulsion tablets (LDET) compared to the plain drug. DSC and XRD studies of the optimized ATV-loaded LDET proved the presence of the drug in the amorphous form. SEM images showed the intact, porous and non-collapsible structure of the prepared LDET with complete loss of ATV crystallinity. Administration of ATV-loaded LDET to high fat diet-induced hyperlipidemic rats demonstrated a significant decrease (p<0.05) in the serum and tissue levels of the tested parameters compared to the market product used. The obtained results suggest a promising, easy-to-manufacture and effective dosage form for the treatment of hyperlipidemia.

In situ forming biodegradable poly(ε-caprolactone) microsphere systems: a challenge for transarterial embolization therapy. In vitro and preliminary ex vivo studies

ABSTRACTBackground: In situ forming biodegradable poly(ε-caprolactone) (PCL) microspheres (PCL-ISM) system was developed as a novel embolic agent for transarterial embolization (TAE) therapy of hepatocellular carcinoma (HCC). Ibuprofen sodium (Ibu-Na) was loaded on this platform to evaluate its potential for the treatment of post embolization syndrome.Methods: The influence of formulation parameters on the size/shape, encapsulation efficiency and drug release was investigated using mixture experimental design. Regression models were derived and used to optimize the formulation for particle size, encapsulation efficiency and drug release profile for TAE therapy. An ex vivo model using isolated rat livers was established to assess the in situ formation of microspheres.Results: All PCL-ISM components affected the studied properties and fitting indices of the regression models were high (Radj2 = 0.810 for size, 0.964 encapsulation efficiency, and 0.993 or 0.971 for drug release at 30 min or 48 h). The optimized composition was: PCL = 4%, NMP = 43.1%, oil = 48.9%, surfactant = 2% and drug = 2%. Ex vivo studies revealed that PCL-ISM was able to form microspheres in the hepatic arterial bed.Conclusions: PCL-ISM system provides a novel tool for the treatment of HCC and post-embolization syndrome. It is capable of forming microspheres with desirable size and Ibu-Na release profile after injection into blood vessels.

Controlling the Release of Indomethacin from Glass Solutions Layered with a Rate Controlling Membrane Using Fluid-Bed Processing. Part 2: The Influence of Formulation Parameters on Drug Release.

This study aimed to investigate the pharmaceutical performance of an indomethacin-polyvinylpyrrolidone (PVP) glass solution applied using fluid bed processing as a layer on inert sucrose spheres and subsequently top-coated with a release rate controlling membrane consisting of either ethyl cellulose or Eudragit RL. The implications of the addition of a pore former (PVP) and the coating medium (ethanol or water) on the diffusion and release behavior were also considered. In addition, the role of a charge interaction between drug and controlled release polymer on the release was investigated. Diffusion experiments pointed to the influence of pore former concentration, rate controlling polymer type, and coating solvent on the permeability of the controlled release membranes. This can be translated to drug release tests, which show the potential of diffusion tests as a preliminary screening test and that diffusion is the main factor influencing release. Drug release tests also showed the effect of coating layer thickness. A charge interaction between INDO and ERL was demonstrated, but this had no negative effect on drug release. The higher diffusion and release observed in ERL-based rate controlling membranes was explained by a higher hydrophilicity, compared to EC.

Development of Transdermal Delivery System of Dexamethasone, Palonosetron and Aprepitant for Combination Antiemetic Therapy

Abstract: Purpose: The objective of this study was to assess the possible transdermal delivery for combination antiemetic therapy of dexamethasone, palonosetron and aprepitant, commonly prescribed in chemotherapy induced nausea and vomiting. Methods: Pluronic lecithin organogel formulation was optimized to incorporate all the three drugs. The influence of formulation parameters like drug concentration (1-5% w/w) and permeation enhancers (oleic acid, n-methyl-2-pyrrolidone, propylene glycol and polyethylene glycol 400) on the transdermal delivery of selected antiemetic agents were evaluated ex vivo. Results: Drug release profiles of dexamethasone, palonosetron and aprepitant from the gels were distinct and biphasic in nature. Higher permeability coefficient was observed in palonosetron, average in dexamethasone and was least in aprepitant. Proportional enhancement in the transdermal fluxes of all the three actives were observed with increase in drug concentrations studied. The highest drug concentrations were further treated with different chemical skin enhancers, which improved (1.2-3.3 folds) the permeability coefficient of actives, but not to the same extent. Greater flux values were observed with oleic acid (for dexamethasone) and propylene glycol (for palonosetron and aprepitant). Concomitant transdermal delivery reduced the flux values (P<0.001) of dexamethasone (9.82 ± 1.39 μg/cm2/h), palonosetron (21.36 ± 1.95 μg/cm2/h) and aprepitant (5.04 ± 0.62 μg/cm2/h), compared to their corresponding values when evaluated individually. Conclusion: This study conclude that the optimized pluronic lecithin organogel could be utilized for the simultaneous transdermal delivery of dexamethasone, palonosetron and aprepitant, which need to be proved further in vivo. Key words: Transdermal, dexamethasone, palonosetron, aprepitant, organogel, enhancer.

Kaempferol loaded lecithin/chitosan nanoparticles: preparation, characterization, and their potential applications as a sustainable antifungal agent

Flavonoid compounds are strong antioxidant and antifungal agents but their applications are limited due to their poor dissolution and bioavailability. The use of nanotechnology in agriculture has received increasing attention, with the development of new formulations containing active compounds. In this study, kaempferol (KAE) was loaded into lecithin/chitosan nanoparticles (LC NPs) to determine antifungal activity compared to pure KAE against the phytopathogenic fungus Fusarium oxysporium to resolve the bioavailability problem. The influence of formulation parameters on the physicochemical properties of KAE loaded lecithin chitosan nanoparticles (KAE-LC NPs) were studied by using the electrostatic self-assembly technique. KAE-LC NPs were characterized in terms of physicochemical properties. KAE has been successfully encapsulated in LC NPs with an efficiency of 93.8 ± 4.28% and KAE-LC NPs showed good physicochemical stability. Moreover, in vitro evaluation of the KAE-LC NP system was made by the release kinetics, antioxidant and antifungal activity in a time-dependent manner against free KAE. Encapsulated KAE exhibited a significantly inhibition efficacy (67%) against Fusarium oxysporium at the end of the 60 day storage period. The results indicated that KAE-LC NP formulation could solve the problems related to the solubility and loss of KAE during use and storage. The new nanoparticle system enables the use of smaller quantities of fungicide and therefore, offers a more environmentally friendly method of controlling fungal pathogens in agriculture.

Depot injectable biodegradable nanoparticles loaded with recombinant human bone morphogenetic protein-2: preparation, characterization, and in vivo evaluation.

ObjectiveThe aim of this study is to utilize the biocompatibility characteristics of biodegradable polymers, viz, poly lactide-co-glycolide (PLGA) and polycaprolactone (PCL), to prepare sustained-release injectable nanoparticles (NPs) of bone morphogenetic protein-2 (BMP-2) for the repair of alveolar bone defects in rabbits. The influence of formulation parameters on the functional characteristics of the prepared NPs was studied to develop a new noninvasive injectable recombinant human BMP-2 (rhBMP-2) containing grafting material for the repair of alveolar bone clefts.Materials and methodsBMP-2 NPs were prepared using a water-in-oil-in-water double-emulsion solvent evaporation/extraction method. The influence of molar ratio of PLGA to PCL on a suitable particle size, encapsulation efficiency, and sustained drug release was studied. Critical size alveolar defects were created in the maxilla of 24 New Zealand rabbits divided into three groups, one of them treated with 5 μg/kg of rhBMP-2 NP formulations.ResultsThe results found that NPs formula prepared using blend of PLGA and PCL in 4:2 (w/w) ratio showed the best sustained-release pattern with lower initial burst, and showed up to 62.7% yield, 64.5% encapsulation efficiency, 127 nm size, and more than 90% in vitro release. So, this formula was selected for scanning electron microscope examination and in vivo evaluation. Histomorphometric analysis showed 78% trabecular bone fill, mostly mature bone in the defects treated with rhBMP-2 in NPs within 6 weeks.ConclusionThe prepared NPs prolonged the release and the residence time of rhBMP-2 in rabbits, which led to the formation of adequate bone in critical size alveolar bone defects in 6 weeks. This noninvasive method has application for the primary restoration of alveolar bone defects.

Formulation Development and Evaluation of Hybrid Nanocarrier for Cancer Therapy: Taguchi Orthogonal Array Based Design

Taguchi orthogonal array design is a statistical approach that helps to overcome limitations associated with time consuming full factorial experimental design. In this study, the Taguchi orthogonal array design was applied to establish the optimum conditions for bovine serum albumin (BSA) nanocarrier (ANC) preparation. Taguchi method with L9 type of robust orthogonal array design was adopted to optimize the experimental conditions. Three key dependent factors namely, BSA concentration (% w/v), volume of BSA solution to total ethanol ratio (v : v), and concentration of diluted ethanolic aqueous solution (% v/v), were studied at three levels 3%, 4%, and 5% w/v; 1 : 0.75, 1 : 0.90, and 1 : 1.05 v/v; 40%, 70%, and 100% v/v, respectively. The ethanolic aqueous solution was used to impart less harsh condition for desolvation and attain controlled nanoparticle formation. The interaction plot studies inferred the ethanolic aqueous solution concentration to be the most influential parameter that affects the particle size of nanoformulation. This method (BSA, 4% w/v; volume of BSA solution to total ethanol ratio, 1 : 0.90 v/v; concentration of diluted ethanolic solution, 70% v/v) was able to successfully develop Gemcitabine (G) loaded modified albumin nanocarrier (M-ANC-G) of size 25.07 ± 2.81 nm (ζ = −23.03 ± 1.015 mV) as against to 78.01 ± 4.99 nm (ζ = −24.88 ± 1.37 mV) using conventional method albumin nanocarrier (C-ANC-G). Hybrid nanocarriers were generated by chitosan layering (solvent gelation technique) of respective ANC to form C-HNC-G and M-HNC-G of sizes 125.29 ± 5.62 nm (ζ = 12.01 ± 0.51 mV) and 46.28 ± 2.21 nm (ζ = 15.05 ± 0.39 mV), respectively. Zeta potential, entrapment, in vitro release, and pH-based stability studies were investigated and influence of formulation parameters are discussed. Cell-line-based cytotoxicity assay (A549 and H460 cells) and cell internalization assay (H460 cell line) were performed to assess the influence on the bioperformance of these nanoformulations.

Effect of process parameters on the properties of some metronidazole tablet and capsule formulations

This work was aimed at evaluating the properties of metronidazole capsules and tablets formulated by different methods in comparison with some commercially available tablet brands to ascertain the influence of formulation parameters and the unpopularity of clinical use of the capsule in Nigeria. Three batches of metronidazole 200 mg tablets were formulated by wet granulation, dry granulation and direct compression methods. Metronidazole 200 mg capsules were formulated by hand filling technique. The formulations and two commercially available tablet brands (M & B, Cardinal) were evaluated following standard procedures. All the formulated tablets passed the uniformity of weight and content, disintegration and dissolution tests but failed the friability test to a significant degree in the order: Dry > Direct Compression > Wet. The release profiles were in the order: Wet > Direct Compression > Dry > M & B > Capsule > Cardinal, with significant (P < 0.05) difference between the highest and the lowest. The results indicated that variations in formulation parameters had important influence on the qualities of solid dosage formulations of metronidazole. Except for one commercial brand, all the tablet formulations tested generally performed better than the capsule formulation, probably supporting its unpopularity in Nigeria. Key words: Metronidazole, capsules, tablets, granulation, dissolution profile.