Influence of chitosan type on the properties of extruded pellets with low amount of microcrystalline cellulose

The purpose of this research was to study the influence of type of chitosan with different molecular weights, ie, 190 and 419 kDa, on properties of pellets prepared by extrusion/ spheronization. The formulations, consisting of acetaminophen as model drug, chitosan, microcrystalline cellulose (MCC), and dibasic calcium phosphate dihydrate with/without sodium alginate, were extruded using a twin-screw extruder and water as the granulating liquid. With 30% wt/wt MCC and no added sodium alginate, spherical pellets were produced containing low and high molecular weight chitosan at a maximum amount of 60% and 40% wt/wt, respectively. With sodium alginate (2.5% wt/wt), pellets with either type of chitosan (60% wt/wt), MCC (17.5% wt/wt), and acetaminophen (20% wt/wt) could be produced indicating an improved pelletforming ability. Type and amount of chitosan and added sodium alginate affected physical properties of pellets including size, roundness, crushing force, and drug release. Low molecular weight chitosan produced pellets with higher mean diameter, sphericity, and crushing force. Additionally, the pellets made of low molecular weight chitosan and added sodium alginate showed faster drug release in 0.1 N HCl but had slower drug release in pH 7.4 phosphate buffer. This indicated that drug release from pellets could be modified by the molecular weight of chitosan. In conclusion, the molecular weight of chitosan had a major influence on formation, physical properties, and drug release from the obtained pellets. Published: August 10, 2007     

Structure and properties of starch-based foams prepared by microwave heating from extruded pellets

The physical properties of microwave-foamed starch-based pellets, including density, porosity, cell structure, water absorption characteristics and mechanical properties were characterized. It was found that the physical properties of these starch-based foams produced by microwave heating are highly dependent on the raw materials and additives. Foam density decreased significantly after addition of 5.5–10.5% w/w salts, while foams containing nucleation agent (talc) were denser than the control with reduced cell size. A proprietary blowing agent did not affect the foam density markedly. Addition of salts also increased the water sorption of foams and plasticized cell walls. Mechanical behaviour of foamed pellets can be adjusted effectively by controlling the cell structure through using different additives. Mechanical properties of the foamed pellets in the elastic region as well as under large deformation (up to 40% strain) all follow a power–law relationship with foam density.     

Evaluation of microcrystalline cellulose prepared from sisal fibers as a tablet excipient: A technical note

Conclusion  The above data demonstrated that MCC derived from sisal fibers could be an industrially feasible alternative for currently used MCCs as diluent and disintegrant for both immediate-release as well as sustained-release oral solid dosage forms. Publshed: February 2, 2007     

Viscoelastic properties of a virucidal cream containing the monoglyceride monocaprin: Effects of formulation variables: A technical note

The viscoelastic properties of the cream formulations were tested by 2 methods (ie, increased stress and increased frequency tests). The rheology experiments indicate that the formulations are stable; they show resistance to external forces, as their elastic properties are sustained whether or not the magnitude or frequency of external forces are increased. The results show that rheological properties of the formulations are affected by the proportion of the oil phase and the amount of carbomer in the aqueous phase, but the effect of monocaprin is modest. Increasing carbomer amount increases viscosity and elasticity. Increasing the oil volume fraction increased the structural stability of the creams. The formulation containing monocaprin, which yielded the most viscoelastic structure was a cream containing 10% oil phase and 0.5% carbomer (Formulation 9).     

Influence of some environmental factors on Rhizopus nigricans submerged growth in the form of pellets

Morphological changes of a steroid transforming filamentous fungus Rhizopus nigricans were studied by altering submerged growth conditions at inoculum sizes previously determined to favor pelleted growth. Beside the main classification between pelleted and clumpy growth forms, the size, concentration and structure of pellets were characterized at different cultivating temperature, initial pH value, medium composition, additives, and aeration conditions. Initial pH below 4 and above 7, the presence of Ca²⁺ and Tween-80 gave rise to the clumpy growth, otherwise pelleted growth prevailed. Among tested factors the pellet size was mainly influenced by the inoculum size and the presence of baffles and Ca²⁺ in cultivation medium. The formation of smooth pellets, prerequisite for further application in the process of steroid biotransformation, resulted in cultivations at lower temperature, high agitation rates in shaken cultures without baffles and at high nitrogen concentration. This revised version was published online in July 2006 with corrections to the Cover Date.     

Determination of aqueous solubility by heating and equilibration: A technical note

Summary and Conclusion  A modified shake-flask solubility method, where the equilibration time was shortened through heating, was used to determine the solubility of 48 different drugs and pharmaceutical excipients in pure water at room temperature. The heating process accelerates dissolution of the solid compound and frequently results in supersaturated solution. Seeding with the solid compound after heating and cooling to room temperature promotes precipitation of the solid compound in its original stable form. This modified shake-flask method generates reliable and reproducible solubility data. Published: January 13, 2006     

Effect of molecular weight of hydrolyzed gelatin on its binding properties in tablets: A technical note

Conclusion  Hydrolyzed gelatins (Byco-A, Byco-O and Byco-C), when used as binders, yielded soft, uniform granules with good flow properties. As the molecular weight and viscosity of hydrolyzed gelatins increased, the compressibility of granules decreased and their compactability increased. The balance between compressibility and compactability of granules may be achieved by careful monitoring of the molecular weight of hydrolyzed gelatins that can serve as potential binders.     

Influence of formulation and process parameters on pellet production by powder layering technique

The goal of the present study was to evaluate the influence of the formulation and operating conditions on pellet preparation by pan technique. To this end, a new pelletization process, typified by the application of powdered drug on sugar-based cores using the GS coating system was studied. Inert cores were intermittently treated with micronized drug powder and adhesive solution. This treatment led to the formation of multiple layers of drug particles around an inert core resulting in the production of pellets that can further be coated by different polymers to obtain modified release formulations. Different procedures have been used to evaluate a series of important parameters such as initial core weight; speed of powder application; speed, type, and position of the atomizers; atomization degree: temperature; and air cap. Good yield of drug layering was obtained by adjusting the quantity of both the drug powder to apply and the binder solution. Pellets obtained following the optimal operating conditions (defined in a pre-formulation study) were film coated with the acrylic polymer Eudragit L30D in order to produce a model formulation consisting of enteric polymer-coated pellets containing ibuprofen. During its preparation, the formulation showed no degradation of the drug, moreover, a low percentage of residual humidity was obtained, indicating that this system is very efficient for the production of highly stable formulations. This study showed the good performance of the GS automated pan-coating system in obtaining enteric coated pellets prepared by powder layering technique using aqueous solutions.     

Clarifications on habitat complexity: A response to technical note by Madin et al.

In a critique of our recent review on measuring habitat complexity in ecology, Madin et al. (2023) advocate the use of fractal dimension in ecology and defend their geometric constraint theory of habitat complexity. We explain the flaws in their arguments and highlight points where they misinterpreted our statements.     

Spherical composite particles of rice starch and microcrystalline cellulose: A new coprocessed excipient for direct compression

Composite particles of rice starch (RS) and microcrystalline cellulose were fabricated by spray-drying technique to be used as a directly compressible excipient. Two size fractions of microcry stalline cellulose, sieved (MCS) and jet milled (MCJ), having volumetric mean diameter (D₅₀) of 13.61 and 40.51 μm, respectively, were used to form composite particles with RS in various mixing ratios. The composite particles produced were evaluated for their powder and compression properties. Although an increase in the microcrystalline cellulose proportion imparted greater compressibility of the composite particles, the shape of the particles was typically less spherical with rougher surface resulting in a decrease in the degree of flowability. Compressibility of composite particles made from different size fractions of microcrystalline cellulose was not different; however, using MCJ, which had a particle size range close to the size of RS (D₅₀=13.57 μm), provided more spherical particles than using MCS. Spherical composite particles between RS and MCJ in the ratio of 7∶3 (RS-MCJ-73) were then evaluated for powder properties and compressibility in comparison with some marketed directly compressible diluents. Compressibility of RS-MCJ-73 was greater than commercial spray-dried RS (Eratab), coprocessed lactose and microcrystalline cellulose (Cellactose), and agglomerated lactose (Tablettose), but, as expected, lower than microcrystalline cellulose (Vivapur 101). Flowability index of RS-MCJ-73 appeared to be slightly lower than Eratab but higher than Vivapur 101, Cellactose, and Tablettose. Tablets of RS-MCJ-73 exhibited low friability and good self-disintegrating property. It was concluded that these developed composite particles could be introduced as a new coprocessed direct compression excipient.     

Studies on effect of pH on cross-linking of chitosan with sodium tripolyphosphate: A technical note

The ionotropic gelation method for formation of crosslinked chitosan particles can be easily modified from ionic cross-linking to deprotonation by adjusting the pH of TPP. Chitosan was cross-linked ionically with TPP at lower pH and by deprotonation mechanism at higher pH. The swelling behavior of cross-linked chitosan appeared to depend on the pH of TPP. The ionically cross-linked chitosan showed higher swelling ability. Thus the nature of crosslinked chitosan can be tailor made to obtain the desired properties in terms of cross-linking density, crystallinity, and hydrophilicity.     

Influence of cultivation conditions on mechanical and morphological properties of bacterial cellulose tubes

Bacterial cellulose (BC) was deposited in tubular form by fermenting Acetobacter xylinum on top of silicone tubes as an oxygenated support and by blowing different concentrations of oxygen, that is, 21% (air), 35%, 50%, and 100%. Mechanical properties such as burst pressure and tensile properties were evaluated for all tubes. The burst pressure of the tubes increased with an increase in oxygen ratio and reached a top value of 880 mmHg at 100% oxygen. The Young's modulus was approximately 5 MPa for all tubes, irrespective of the oxygen ratio. The elongation to break decreased from 30% to 10-20% when the oxygen ratio was increased. The morphology of the tubes was characterized by Scanning Electron Microscopy (SEM). All tubes had an even inner side and a more porous outer side. The cross section indicated that the tubes are composed of layers and that the amount of layers and the yield of cellulose increased with an increase in oxygen ratio. We propose that an internal vessel wall with high density is required for the tube to sustain a certain pressure. An increase in wall thickness by an increase in oxygen ratio might explain the increasing burst pressure with increasing oxygen ratio. The fermentation method used renders it possible to produce branched tubes, tubes with unlimited length and inner diameters. Endothelial cells (ECs) were grown onto the lumen of the tubes. The cells formed a confluent layer after 7 days. The tubes potential as a vascular graft is currently under investigation in a large animal model at the Centre of Vascular Engineering, Sahlgrenska University     

A preliminary pharmacokinetic study of liposomal leuprolide dry powder inhaler: A technical note

Summary and Conclusions  The developed liposomal DPI of LEU (LLEUn-DPI) demonstrated approximately 50% bioavailability compared with SC route. The studies justify the role of the pulmonary route as a promising alternative to the presently available SC route. The components of liposomal vesicles may be suitably changed to achieve higher bioavailability. Pulmonary delivery of LEU is expected to help in improving patient compliance, self-administration and avoiding the complications related to injection procedure. The developed LEU-DPI may be employed for both male and female contraception and treatment of prostate cancer in men and early puberty in children. In women it may be used for ovarian, endometrial, pancreas, and breast cancer; endometriosis; Uterine Leiomyoma; and anemia due to uterine fibroid tumors. However, the role of LEU-DPI in clinical practice can only be justified only after in vivo studies on 2 species of animals followed by extensive clinical trials. Published: October 24, 2005     

Cryoprotective effect of antifreeze polyamino-acid (Carboxylated Poly-l-Lysine) on bovine sperm: A technical note

In this study, investigating Carboxylated Poly-l-Lysine (CPLL) for its effectiveness as a new cryoprotectant for bovine sperm is aimed. CPLL is an ampholytic polymer compound, has cryoprotective properties similar to those of anti-freeze protein. The cryopreservation medium used for control group consisted of 6.5% (v/v) glycerol, the cryopreservation medium used for experimental group consisted of 3.25% (v/v) glycerol + 0.5% (w/v) CPLL. There was no consequential difference in sperm motility parameter after thawing whereas there was huge distinction for sperm membrane integrity rate (control vs experimental; 49.6 vs 60.7%, P < 0.01). Conception rate of artificial insemination of experimental group was significantly higher than that of control group (79.0% vs 53.1%, P < 0.01). These results suggest CPLL has protected sperm membrane and leads to improve fertility. This is the first report using CPLL for bovine sperm cryopreservation, it is also expected CPLL can be applied to other animal species.     

Studies on spray-dried mixtures of chitosan and hydrolyzed gelatin as tablet binder: A technical note

Conclusion  The results of this investigation showed that spray drying of CH and HG resulted in free-flowing powder, which exhibited improved compressibility and compactibility, thereby suggesting the potential of such spray-dried mixtures of CH and HG as binder in tablets. Optimization of CH:HG ratio needs to be undertaken on a case basis, depending on the presence of other excipients in the formulation. Published: October 22, 2005     

Liposome formulation of NSC-639829 using halothane as a solvent: A technical note

Conclusion  Halothane has been successfully used as a solvent for the liposome formulation of NSC-639829. Liposomes with similar morphology, particle size, incorporation efficiency, and stability were obtained with halothane, chloroform, and ether. Halothane provides additional ease in formulation because of its higher volatility and safety as compared with chloroform and ether. Halothane can be regarded as a safe alternative to chloroform or ether in liposome formulation.     

Estimation of intramolecular cyclization activation energies via isothermal gravimetric analysis: A technical note

Summary and Conclusion  Isothermal gravimetric analysis was used to monitor the weight loss of 4 exploratory compounds as an indicator of their solid-state thermal stability. Data obtained from TGA were further processed via a model-free isoconversional method to estimate the activation energy values. These values ranged from 140 to 218 kJ/mol and were inversely related to their corresponding surface areas. Based on their activation energy values, the relative stability of these 4 exploratory compounds can be ranked as C>D>B>A and their formulation development activities can be prioritized. Published: August 4, 2006