Ajaz S. Hussain

Application of Neural Computing in Pharmaceutical Product Development

Neural computing technology is capable of solving problems involving complex pattern recognition. This technology is applied here to pharmaceutical product development. The most commonly used computational algorithm, the delta back-propagation network, was utilized to recognize the complex relationship between the formulation variables and the in vitro drug release parameters for a hydrophilic matrix capsule system. This new computational technique was also compared with the response surface methodology (RSM). Artificial neural network (ANN) analysis was able to predict the response values for a series of validation experiments more precisely than RSM. ANN may offer an alternative to RSM because it allows for the development of a system that can incorporate literature and experimental data to solve common problems in the pharmaceutical industry.

Application of Neural Computing in Pharmaceutical Product Development: Computer Aided Formulation Design

AbstractMost pharmaceutical products are complex systems designed to meet several compendial or other performance standards simultaneously. Ideal or ‘optimum’ product composition and the manufacturing process variables are generally established after extensive experimentation. Artificial Neural Networks are pattern recognition tools that allow the development of ‘expert’ systems without having to write computer programs. With this technology it may be possible to develop formulation ‘expert’ systems to predict the formulation composition and the manufacturing process conditions necessary to achieve the desired performance standards. This report introduces the concept of a formulation expert system to predict the in vitro drug release profile from hydrophilic matrix tablets. Formulation expert systems or Computer Aided Formulation Design has the potential to reduce the time and cost of the product development process.

Transdermal delivery of tacrine: I. Identification of a suitable delivery vehicle

Abstract Peroral administration of tacrine, a drug approved for the treatment of Alzheimers disease, is associated with low bioavailability (due to first-pass effect), short elimination half-life and reversible hepatotoxicity. Transdermal administration may reduce the degree of these problems. In this investigation the influence of three commonly used solvents (water, propylene glycol and ethanol), and their mixtures, on the in vitro permeation of tacrine through rat and human skin were evaluated. Maximum flux and permeability were observed from ethanol-propylene glycol and water-ethanol binary mixtures, respectively. The permeability of tacrine through rat skin was about 2.5 times higher than that through human skin. Excellent correlation between the rat and human skin data was observed. The flux from the ethanol-propylene glycol binary mixture was 98 μg/cm 2 per h through rat skin and was selected for in vivo transdermal administration. The observed in vivo tacrine plasma concentrations were in good agreement with the concentration-time profile simulated using in vitro flux and tacrine clearance in rat. Preliminary short-term (24 h) irritation studies did not indicate any irritation. The results from this investigation indicate that transdermal delivery of tacrine may be feasible and that the ethanol-propylene glycol (1:1) mixture appears to be a promising solvent system.

Effects of Blending a Nonionic and an Anionic Cellulose Ether Polymer on Drug Release from Hydrophilic Matrix Capsules

Blends of hydroxyethylcellulose (HEC) and sodium carboxymethylcellulose (NaCMC) were used to achieve zero order release of chlorpheniramine maleate (CM) from hydrophilic matrix capsules. Dynamic swelling/erosion and response surface measurements were made to provide an insight into the drug release behavior. The drug to total polymer and the HEC to NaCMC ratio influences the rate of drug release. NaCMC appears to influence water uptake and erosion of the matrix mixture. The factors by which zero-order drug release is achieved may include synchronization of the rates of water uptake and polymer erosion even though a constant diffusional pathlength may not be maintained. The combined mixture factorial design presented in this study allows for the characterization and optimization of the drug release profiles.

Draft Guidance for Industry Extended-Release Solid Oral Dosage Forms

This draft guidance provides recommendations to pharmaceutical scientists related to various aspects of in vitro/in vivo correlations (IVIVC) for oral extended-release (ER) drug products particularly as utilized in the NDA/ANDA review process. It presents a comprehensive perspective on methods of developing IVIVC, appropriate means of evaluating the predictability of IVIVC, and relevant applications for IVIVC in the areas of changes (e.g., formulation, equipment, process, and manufacturing site) and setting dissolution specifications. To access the final guidance on the WWW, connect to theFDA home page at http://www.fda.gov/CDER/ and go to the “Regulatory Guidance” section.

Age-related digoxin effects in an intact canine model

The inotropic and electrophysiologic effects of digoxin were studied in anesthetized neonatal and adult dogs to test the hypothesis that digoxin had comparable effects in these groups. Recordings of the ECG and central arterial pressure were made starting at 5.75 hours after an intravenous injection of 50 micrograms/kg of the drug. Parameters measured were heart rate (HR); PR interval; mean, systolic, and diastolic blood pressure; preejection period (PEP); and ejection time (ET). Two indices of systolic function were calculated, the systolic time interval (STI = PEP/ET) and total electromechanical systole (TMS = PEP + ET), which was indexed for HR. There was no significant difference from control animals in either the adult or neonatal groups in the PR interval or blood pressure. In the neonatal dogs, HR and STI were also not significantly different from control. However, in the neonatal dogs, there was a significant decrease in the indexed TMS, 288 +/- 7 vs 270 +/- 11 msec (p less than 0.01). In the adult animals, HR decreased from 116 +/- 35 to 66 +/- 25 bpm (p less than 0.01), STI decreased from 0.559 +/- 0.059 to 0.447 +/- 0.069 (p less than 0.01), and indexed TMS decreased from 333 +/- 10 to 291 +/- 13 msec (p less than 0.001). Two-way analysis of variance demonstrated that digoxin differed significantly in its effects on HR (p = 0.005), STI (p = 0.018), and TMS indexed for HR (p = 0.003) in neonatal compared to adult dogs. Pharmacokinetic studies showed a rapid distribution phase and equilibrium conditions at the time of physiologic measurements.(ABSTRACT TRUNCATED AT 250 WORDS)