Biomedical subjects

S A Altaf

Publications and source records attributed to S A Altaf.

6 recordsLinked to original sources

PubMed1999

Bead compacts. II. Evaluation of rapidly disintegrating nonsegregating compressed bead formulations.

In this study, three techniques for the prevention or mitigation of polymer coat fracture on compaction of sustained-release beads into tablets were investigated. All techniques in this paper were evaluated without the addition of any cushioning excipients, but rather by spray coating these excipients to avoid segregation during product manufacturing. First, it was shown that use of swellable polymers such as polyethylene oxide (PEO) serves a unique and effective role in preventing polymer coat rupture. PEO was spray coated between the ethylcellulose (EC) and microcrystalline cellulose (MCC) coats to evaluate its cushioning effect. The compacted PEO layered beads, on dissolution, disintegrated into individual beads with sustained drug release of up to 8 hr. It is postulated that the PEO was hydrated and formed a gel that acts as a sealant for the cracks formed in the ruptured polymer coating (sealant-effect compacts). Second, EC-coated drug-layered beads were also overcoated with cushioning excipients such as polyethylene glycol (PEG) and MCC with an additional coating of a disintegrant. These beads were compressed at pressures of 125, 500, and 1000 pounds into caplets and, on dissolution testing, disintegrated into individual beads when the dissolution medium was switched from simulated gastric to intestinal fluid. The dissolution profiles show that the polymer coat was partly disrupted on compaction, leading to a total drug release in 8-10 hr. Third, EC-coated beads were also granulated with cushioning excipient and compressed.

Chemistry, Pharmaceutical↗

PubMed1998

Guar gum-based sustained release diltiazem.

PURPOSE: This study was performed to examine the use of guar gum to sustain the release of diltiazem under in vitro and in vivo conditions. METHODS: Guar gum tablet formulations were prepared and evaluated under a variety of in vitro dissolution conditions. The formulations, along with Dilacor XR, were administered to a group eight fasted, healthy volunteers in a four period crossover study. RESULTS: Varying the lot of guar gum as well as using guar from different suppliers had little effect on diltiazem dissolution. Also, dissolution of diltiazem from guar gum tablets was essentially independent of stir speed under normal conditions (USP Apparatus II) The stability of guar-based formulations under stressed conditions (40 degrees C/75% relative humidity for 3 months) was also established. All four formulations gave similar plasma concentrations over time in the healthy volunteers pharmacokinetic study. CONCLUSIONS: Guar gum-based matrix tablets represent a simple and economical alternative to existing diltiazem sustained release dosage forms.

Antihypertensive Agents↗

PubMed1998

Optimization of sustained-release diltiazem formulations in man by use of an in-vitro/in-vivo correlation.

In-vitro/in-vivo correlations (IVIVC) are useful for predicting in-vivo results from in-vitro data. An IVIVC has been used to optimize a hydrocolloidal-based matrix tablet designed to be bioequivalent to an existing once-daily diltiazem HC1 product (Dilacor XR 240mg; Rhone-Poulenc Rorer). Data from a preliminary formulation dosed to fasted and fed subjects were used to establish the IVIVC. The correlation was then used during reformulation of the dosage forms to predict changes in the maximum plasma concentration (Cmax) and the area under the plasma-concentration-time curve (AUC) for fasted and fed subjects using in-vitro dissolution data. The IVIVC adequately predicted plasma profiles of two optimized formulations in studies with fasted and fed subjects.

Cardiovascular Agents↗

PubMed1998

Bead compacts. I. Effect of compression on maintenance of polymer coat integrity in multilayered bead formulations.

Little information is available on the compactability of beads for oral sustained-release dosage forms. It is known that polymer-coated beads may fuse together to produce a non-disintegrating controlled-release matrix tablet when compressed. This study evaluates the effect of compression on beads with multiple layers of polymer and drug coat, and the effect of cushioning excipients and compaction pressure on drug release from compressed bead formulations. The multilayered beads consist of several alternating layers of acetaminophen (APAP) and polymer coats (Aquacoat) with an outer layer of mannitol as a cushioning excipient. Percent drug release versus time profiles showed that the release of drug decreases from noncompacted beads as the amount and number of coatings increases, with only 43% of drug released in 24 hr for coated beads with 10 layers. It was shown that the compacted multilayered beads will disintegrate in gastrointestinal fluids, providing a useful drug release pattern. It was shown that beads of drug prepared by any method can be spray-layered with excipients such as Avicel and mannitol. Spray-layering of the cushioning excipient onto beads can provide an effective way to circumvent segregation issues associated with mixing of the polymer-coated beads and powdered or spherical/nonspherical cushioning excipients. Spray layering of the cushioning excipient can also provide excellent flow properties of the final formulation as visually observed in our experiments. Triple-layered caplets (TLC) were also prepared with outer layers of Avicel PH-101 or polyethylene oxide (PEO), and a center layer of polymer-coated beads. For TLC, the polymer coating on the beads fractured, and nondisintegrating matrix formulations were obtained with both caplet formulations.

Cellulose↗

PubMed1997

Theory of force transducer design optimization for die wall stress measurement during tablet compaction: optimization and validation of split-web die using finite element analysis.

PURPOSE: 1) To illustrate how computer aided engineering stress analysis can be used to improve the transducer design process for tablet press instrumentation; 2) to use these optimal design procedures for the geometric optimization of a cylindrical, segmented, and a novel split-web die design. Discussion includes the selection of optimal die wall thickness, segment cutting angle, strain gage placement, Wheatstone bridge configuration, and the influence of tablet height and position within the die on signal output. METHODS: Stress analysis was done with a finite element analysis (FEA) software package running on a personal computer. RESULTS: For the segmented die, the admissible range of die wall thicknesses depends upon cutting angle; the signal output is non-linear because the stress distribution in the die wall is influenced by tablet height and position within the die. For the split-web die, the optimal configuration consists of a 1/8 in. sensing web with a strain gage located at the peak of the sensing-web arch. This prototype had a linear calibration curve (r2 = 0.999) with no hysteresis. Radial versus axial stress transmission curves for: starch and sodium chloride were consistent with literature data. CONCLUSIONS: Finite element analysis (FEA) is a useful numerical tool for the systematic optimization of tablet press instrumentation. By enclosing the sensing web of a three layered die design in a cylinder, the split-web design can be directly mounted without modification of the die table.

Drug Design↗

PubMed1995

Deformation of the Stokes B2 rotary tablet press: quantitation and influence on tablet compaction.

Deformations that affect the vertical punch displacement of a Stokes B2 rotary tablet press were characterized with a cathetometer. The press deformation was found to be elastic for both the upper and lower compression roller assemblies. However, the upper and lower compression roller assemblies have different Hookian spring constants: 8.58 x 10(4) and 5.18 x 10(4) kN/m for the upper and lower assemblies, respectively. Using two-way analysis of variance, the Hookian spring constants were shown to be independent of compaction phases and lower punch penetration setting. To study the influence of press deformation on tablet compaction, the Hookian spring constants were factored into the caculation of the incremental work of compaction for dibasic calcium phosphate dihydrate and microcrystalline cellulose. As the peak compression pressure increases, the force-displacement work done on the tablet during the loading phase decreases relative to calculations that neglect press deformation. This decrease in force-displacement work was attributed to elastic press deformation, which absorbs energy during the loading phase and then releases this energy later in the compaction cycle, altering the punch-displacement profile. The rate at which the press stores and releases elastic energy depends in part upon the viscoelastic properties of the tablet. Based upon these results, the coupling between press elasticity and a tablet's viscoelastic properties should be accounted for when analyzing tablet compaction or trying to simulate the punch-displacement profile of a tablet press that deforms during compaction.

Chemistry, Pharmaceutical↗