Drum Dried Waxy Maize Research Articles

Influence of deposition and spray pattern of nasal powders on insulin bioavailability

The influence of the deposition pattern and spray characteristics of nasal powder formulations on the insulin bioavailability was investigated in rabbits. The formulations were prepared by freeze drying a dispersion containing a physical mixture of drum dried waxy maize starch (DDWM)/Carbopol ® 974P (90/10, w/w) or a spray-dried mixture of Amioca ® starch/Carbopol ® 974P (25/75, w/w). The deposition in the nasal cavity of rabbits and in a silicone human nose model after actuation of three nasal delivery devices (Monopowder, Pfeiffer and experimental system) was compared and related to the insulin bioavailability. Posterior deposition of the powder formulation in the nasal cavity lowered the insulin bioavailability. To study the spray pattern, the shape and cross-section of the emitted powder cloud were analysed. It was concluded that the powder bulk density of the formulation influenced the spray pattern. Consequently, powders of different bulk density were prepared by changing the solid fraction of the freeze dried dispersion and by changing the freezing rate during freeze drying. After nasal delivery of these powder formulations no influence of the powder bulk density and of the spray pattern on the insulin bioavailability was observed.

Characterization and in vivo evaluation of ocular minitablets prepared with different bioadhesive Carbopol–starch components

The purpose of this study was to evaluate different bioadhesive ocular formulations based on drum dried waxy maize ® starch (DDWM), Amioca ® starch and Carbopol ® 974P. The concentrations of Carbopol ® 974P in the mixtures varied between 5 and 25% (w/w). The rheological properties of the non-sterilized and gamma-irradiated physical blends of Carbopol ® 974P with either DDWM or Amioca ® were compared to those of the corresponding co-spray dried Amioca ® starch/Carbopol ® powders. Higher viscosity or consistency values were measured for sterilized co-spray dried powder mixtures containing an amount of Carbopol ® 974P equal or above 15% (w/w) compared to the physical blends. Sustained release minitablets (Ø 2 mm, 6 mg), consisting of sodium fluorescein as model drug and the bioadhesive powders, were manufactured at a compression force of 1.25 kN. Afterwards, the tablets were sterilized with gamma-irradiation. The amount of Carbopol ® in the co-spray dried powder mixtures on the one hand and gamma-irradiation on the other hand had no significant influence on the crushing strength and friability of the minitablets evaluated. However, these two factors affected the in vitro release properties of the minitablets. The slowest release was obtained with tablets containing 25% Carbopol ® 974P, which unfortunately possess mucosal irritating properties. By using co-spray dried Amioca ® with 15% (w/w) Carbopol ® 974P, a slower release can be achieved compared to the physical mixtures of DDWM or Amioca ® starch with Carbopol ® 974P. Moreover, this ocular formulation is very promising and is preferred, as it did not cause any mucosal irritation and released the model drug for at least 12 h, after application in the fornix.

Effects of roller compaction settings on the preparation of bioadhesive granules and ocular minitablets

An experimental factorial design was employed to evaluate bioadhesive granules and bioerodible ocular minitablets (6 mg and Ø 2 mm). The purpose of this study was to compare minitablets prepared using roller compacted granules with an optimised minitablet formulation, manufactured on laboratory scale by direct compression. The formulation consisted of drum dried waxy maize starch, Carbopol ® 974P, and ciprofloxacin in a ratio of 90.5/5/3 (w/w/w). Three roller compactor parameters were varied, i.e. the roller speed, the horizontal screw speed and the compaction force, while the vertical screw speed was kept constant. Afterwards, the ribbons were milled to obtain granules suitable for compression. The friability, the flow properties, the bulk material characteristics (apparent and tap density and porosity) and the particle size distributions of two granule sieve fractions (90–125 and 125–355 μm) were investigated. The roller speed and the compaction force have the largest influence on the granule characteristics, followed by the horizontal screw speed. The physical properties of non- and gamma-irradiated minitablets were determined. From the tablet strength, friability and dissolution results, a low compaction force and a high roller speed were shown to be preferable to prepare granules which can be further tabletted into adequate ocular minitablets.

Rheological study on mucoadhesivity of some nasal powder formulations

Various powder mixtures were used to administer insulin via the nasal route: a co-spray dried mixture of Amioca ® starch and Carbopol ® 974 P (1/3), drum dried waxy maize starch and Carbopol ® 974 P (9/1), maltodextrin DE38/Carbopol ® 974 P (9/1) and pure drum dried waxy maize starch. Oscillatory rheology is performed to study and compare the viscosity, elasticity and mucoadhesivity of these powder formulations. There was no rheological synergism detectable with the co-spray dried mixture of Amioca ® starch and Carbopol ® 974 P (1/3), drum dried waxy maize starch and Carbopol ® 974 P (9/1) and maltodextrin DE38/Carbopol ® 974 P (9/1). Interaction due to entanglements was seen with drum dried waxy maize starch (100%). The differences in nasal bioavailability between the different carriers could be explained by differences in G′ (storage modulus, elasticity) and G″ (loss modulus, viscosity) values. The formulation giving the highest bioavailability, provided also the highest G′ and G″ values.

Influence of multiple nasal administrations of bioadhesive powders on the insulin bioavailability

Peptides and more especially insulin are mainly used in therapies that need multiple drug administration. As peptides are highly potent, it is required that their bioavailability remains constant even during a long term administration. In this study, the bioavailability and blood glucose levels are reported after multiple nasal administration of insulin via two bioadhesive platforms consisting of a cospray dried mixture of Amioca® starch and Carbopol® 974P (1/3) and a physical mixture of drum dried waxy maize starch and Carbopol® 974P (9/1), respectively. The experiments were performed in rabbits and the formulations were administered during 8 consecutive days. The bioavailability and the maximal decrease of the blood glucose level were determined on the first and last day of the insulin administration. These two parameters were decreased on the eighth day compared with the first day of administration. When the formulations were not administered from day 2 until day 7, the bioavailability on the eighth day compared with the first day of administration was not modified. It was concluded that daily administrations of the bioadhesive formulations affected the nasal bioavailability of insulin in rabbits.

Evaluation of a mucoadhesive tablet for ocular use

The present study investigates the use of a polymer mixture containing Carbopol 974P and drum dried waxy maize starch to obtain prolonged drug release to the anterior eye segment. Two dosage forms with this composition are compared: a hydrated polymer dispersion and a minitablet. A model fluorescent tracer is used to study the ocular release and diffusion from the two dosage forms in humans. To evaluate the prolongation in the cornea/tearfilm compartment, the Apparent Fluorescein TurnOver (%/min) is calculated. The parameters C max, t max, and C 9h are used to characterize the pharmacokinetics of Na-fluorescein in the anterior chamber. Furthermore, the swelling behavior of the minitablet is evaluated macroscopically, while the degree of interaction with mucin is characterized by rheological measurements. Calculation of an acceptability score and a slug irritation potential is performed to evaluate user acceptability. In contrast to the hydrated dispersion, the minitablet significantly decreases the Apparent Fluorescein TurnOver (%/min) ( P<0.05) and increases the apparent fluorescence in the anterior chamber 9 h after application of the preparation. Rheological data demonstrate the presence of elastic interactions between the polymer and mucin. The dry core of the minitablet becomes fully hydrated after approximately 2 h and is subsequently transformed into a highly concentrated gel. The acceptability of the minitablet is comparable to that of the polymer dispersion. Prolonging the release of Na-fluorescein to the anterior eye segment is only feasible with the dry preparation.

Toxicological evaluation of a bioadhesive nasal powder containing a starch and Carbopol ® 974 P on rabbit nasal mucosa and slug mucosa

The purpose of this study is the investigation of possible adverse effects of a powder formulation containing drum-dried waxy maize (DDWM) starch and Carbopol ® 974 P (90/10) on the nasal mucosa of rabbits and the foot mucosa of slugs after multiple administrations. In the rabbit, the effect of the formulation was measured by the release of proteins and lactate dehydrogenase (LDH) from the nasal mucosa with a new non-invasive in vivo method and also by histopathology. The mucosal toxicity of the formulation was evaluated using slugs by measuring the effect on the body weight and the amount of mucus produced during a repeated contact period. Additionally, the release of proteins, lactate dehydrogenase and alkaline phosphatase from the body wall of the slugs after a repeated treatment was measured. Twenty four hours after the powder administration to the rabbits the release of the marker molecules was comparable with the negative controls. The histopathological study showed only a slight increase of granulocytes in the epithelium. The formulation induced a higher mucus production in the slugs but no additional effects were detected on the body weight and on the release of proteins. No enzymes were released from the body wall. The results indicate that the effect of the bioadhesive powder consisting of DDWM/Carbopol ® 974 P (90:10, w/w) on the mucosa was negligible.

Evaluation of starch–maltodextrin–Carbopol ® 974 P mixtures for the nasal delivery of insulin in rabbits

In this study insulin was administered nasally to rabbits as a dry powder formulation. The powders consisted of drum-dried waxy maize starch (DDWM) or maltodextrins with different DE values and Carbopol ® 974 P. The powders were prepared by freeze-drying a dispersion of these excipients with insulin. Bioavailabilities obtained with the powder formulations containing DDWM/Carbopol ® 974 P (5 and 10%) were significantly higher ( p<0.05) than those containing maltodextrins–Carbopol ® 974 P mixtures. The bioavailability of the powder formulation containing DDWM and 10% Carbopol ® 974 P was significantly higher (14.4%) than the bioavailability of the same mixture containing 5% Carbopol ® 974 P (9.9%). The bioavailability, t max and C max values of the formulation with 5% Carbopol ® 974 P were significantly higher in comparison with the formulation without Carbopol ® 974 P. 10% Carbopol ® 974 P was required when maltodextrins were used in order to obtain a significantly higher bioavailability compared with the formulations without Carbopol ® 974 P. Freeze-drying seemed a prerequisite for a good bioavailability from the powder formulation as well as the ratio of insulin versus bioadhesive powder (1 IU and 2 IU/mg of bioadhesive powder).

Formulation development and in vivo evaluation of a novel bioadhesive lozenge containing a synergistic combination of antifungal agents

Two novel bioadhesive antifungal lozenges were developed. Both were two-layered with an upper modified-release drug-containing layer and a lower bioadhesive layer composed of drum-dried waxy maize starch and Carbopol 980 to facilitate application to the oral mucosa. The first type of lozenge contained miconazole nitrate as a spray-dried form containing acacia and Cremophor RH40 to increase the dissolution of the poorly soluble azole, plus flavourings. The second type also contained chlorhexidine acetate in the drug layer, as both drugs had been reported to act synergistically. In vivo release of drug(s) into saliva was assessed in a group of healthy volunteers, with the lozenges located in an upper posterior site in the oral cavity. Therapeutic levels were achieved for extended periods of time with both formulations. Intra-subject variation was greater than inter-subject variation. By examining salivary drug concentrations obtained when the second formulation was applied to an upper anterior location, the release of drugs was shown not to be significantly affected by the location within the oral cavity. In comparison to a proprietary oral gel formulation, the new bioadhesive lozenges produced much more uniform and effective salivary levels of miconazole nitrate over a prolonged period.

Instrumentation of a roll compactor and the evaluation of the parameter settings by neural networks

A Fitzpatrick L83 Chilsonator was instrumented in order to understand and to optimize the roll compaction process using drum-dried waxy maize starch, a plastic deforming material as a model compound. The interrelation of the four adjustable roll compactor parameter settings namely the velocity of the rolls (RS), the speed of the horizontal (HS) and of the vertical screw (VS), and the air pressure (P air) influenced the compact and the granule quality. The granule quality was defined by the friability and particle size distribution. As a second order polynomial was not successful to model the behaviour of the friability in function of the four roll compactor parameters, a Multilayer Feed-Forward neural network (MLF) was used. It was shown that the MLF network models the friability more accurately than a second order polynomial. The HS and the P air mostly influenced granule quality and should be kept at a high level. The VS had no significant influence on compact quality.

Instrumentation of a roll compactor and compaction of drum-dried waxy maize starch & lactose

Instrumentation of a roll compactor and compaction of drum-dried waxy maize starch & lactose

In-vitro bioadhesion of a buccal, miconazole slow-release tablet.

The bioadhesive characteristics of thermally modified starch/polyacrylic acid (PAA) tablets, containing miconazole nitrate, were determined. The detachment force and work of adhesion were significantly affected by the ratio of drum-dried waxy maize starch and PAA. Pure PAA showed the highest detachment force and work of adhesion while the lowest force and work of adhesion were observed for pure starch. There was a pronounced effect of molecular weight of PAA on the bioadhesive characteristics. Miconazole nitrate did not influence bioadhesion up to a concentration of 30%. The influence of additives was negligible and fluctuations of pH did not influence the bioadhesive strength of the tablet.

In vitro/in vivo correlation of the bioadhesive properties of a buccal bioadhesive miconazole slow-release tablet.

An in vitro-in vivo correlation study was performed on the bioadhesive properties of three buccal formulations based on modified starch (drum-dried waxy maize)/polyacrylic acid mixtures. Mixtures containing 10 mg miconazole nitrate, characterized by a different in vitro detachment force and work of adhesion, were evaluated for their bioadhesive properties in human volunteers. The results obtained showed that no significant difference could be seen among the formulations in vivo. The in vitro method showed no significant influence of miconazole nitrate on the bioadhesion properties of the polymers, while the in vivo adhesion time of the pure polymer mixtures was significantly higher than for the polymers containing miconazole. The results from the in vitro method thus did not correlate well with the in vivo data. The in vitro method provided information only on the initial bioadhesion and no correlation could be made with the residence time of the tablet in the oral cavity.

Chronopharmacokinetic considerations in the design of ocular drug delivery systems

An experimental factorial design was employed to evaluate bioadhesive granules and bioerodible ocular minitablets (6 mg and Ø 2 mm). The purpose of this study was to compare minitablets prepared using roller compacted granules with an optimised minitablet formulation, manufactured on laboratory scale by direct compression. The formulation consisted of drum dried waxy maize starch, Carbopol® 974P, and ciprofloxacin in a ratio of 90.5/5/3 (w/w/w). Three roller compactor parameters were varied, i.e. the roller speed, the horizontal screw speed and the compaction force, while the vertical screw speed was kept constant. Afterwards, the ribbons were milled to obtain granules suitable for compression. The friability, the flow properties, the bulk material characteristics (apparent and tap density and porosity) and the particle size distributions of two granule sieve fractions (90–125 and 125–355 μm) were investigated. The roller speed and the compaction force have the largest influence on the granule characteristics, followed by the horizontal screw speed. The physical properties of non- and gamma-irradiated minitablets were determined. From the tablet strength, friability and dissolution results, a low compaction force and a high roller speed were shown to be preferable to prepare granules which can be further tabletted into adequate ocular minitablets.