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Michael J Akers

Publications and source records attributed to Michael J Akers.

7 recordsLinked to original sources
PubMed2006

Rapid determination of dry layer mass transfer resistance for various pharmaceutical formulations during primary drying using product temperature profiles.

Mass transfer resistance of the dry layer during the primary drying phase of a lyophilizaton cycle is probably the most important factor affecting maximum product temperature and drying time. Product resistance parameters should be determined for each formulation because of their dependence of formulation composition and concentration. The purpose of this study was to determine the dry layer mass transfer resistance, using a simple and rapid method, for various pharmaceutical formulations during primary drying in a laboratory dryer, using monitored product temperature profiles. The mathematical tools used for the determination were a primary drying simulation program in conjunction with Powell's optimization algorithm. For each formulation studied, primary drying was performed using a shelf temperature of -15 or -20 degrees C and the chamber pressure controlled at 100 mTorr (0.1 Torr). The product temperature profiles (T(b)) during primary drying were recorded and became the input data for the parameter estimation. The normalized product resistance, R(pN), as a function of the dry layer thickness, l, can be described by: R(pN) = R(0) + A(1)l/(1 + A(2)l), where the constants R(0), A(1) and A(2) are product resistance parameters of water vapor through the dry layer. Even when the parameter A(1) was negative, indicating that product temperature atypically decreased over time, the dry layer product resistance parameters of the various pharmaceutical formulations could be rapidly and successfully determined using the proposed approach. The product resistance equation obtained in this work for 5% marmitol, expressed as R(pN) = 0.0002025 + 20.23l, is similar to that obtained by Pikal [Pikal, M.J., 1985. Use of laboratory data in freeze drying process design: heat and product resistance parameters and the compute simulation of freeze drying. J. Parent. Sci. Technol. 39, 115-138.] using the microbalance method, expressed as R(pN) = 1.40 + 16.0l. The product resistance values obtained for the 3% lactose-LDH formulation are also very close to those obtained by (Milton, N., Pikal, M.J., Roy, M.L., Nail, S.L., 1997. Evaluation of manometric temperature measurement as a method of monitoring product temperature during lyophilization. PDA J. Pharm. Sci. Technol. 51, 7-16.) for 5% lactose using the MTM (manometric temperature measurement) method. With the obtained values of the parameters R(0), A(1), and A(2), simulations can be performed to determine the maximum product temperature and the drying time during primary drying. As such, optimum cycle parameters can be determined to avoid collapse of the product. The proposed approach requires only accurately measured product temperature profiles, easily obtained in a laboratory dryer.

Algorithms↗
PubMed2005

Correlation of laboratory and production freeze drying cycles.

The purpose of this study was to develop the correlation of cycle parameters between a laboratory and a production freeze-dryer. With the established correlation, key cycle parameters obtained using a laboratory dryer may be converted to those for a production dryer with minimal experimental efforts. In order to develop the correlation, it was important to consider the contributions from the following freeze-drying components: (1) the dryer, (2) the vial, and (3) the formulation. The critical parameters for the dryer are the shelf heat transfer coefficient and shelf surface radiation emissivity. The critical parameters for the vial are the vial bottom heat transfer coefficients (the contact parameter Kcs and separation distance lv), and vial top heat transfer coefficient. The critical parameter of the formulation is the dry layer mass transfer coefficient. The above heat and mass transfer coefficients were determined by freeze-drying experiments in conjunction with mathematical modeling. With the obtained heat and mass transfer coefficients, the maximum product temperature, Tbmax, during primary drying was simulated using a primary drying subroutine as a function of the shelf temperature and chamber pressure. The required shelf temperature and chamber pressure, in order to perform a successful cycle run without product collapse, were then simulated based on the resulting values of Tbmax. The established correlation approach was demonstrated by the primary drying of the model formulation 5% mannitol solution. The cycle runs were performed using a LyoStar dryer as the laboratory dryer and a BOC Edwards dryer as the production dryer. The determined normalized dried layer mass transfer resistance for 5% mannitol is expressed as RpN=0.7313+17.19l, where l is the receding dry layer thickness. After demonstrating the correlation approach using the model formulation 5% mannitol, a practical comparison study was performed for the actual product, the lactate dehydrogenase (LDH) formulation. The determined normalized dried layer mass transfer resistance for the LDH formulation is expressed as RpN=4.344+10.85l. The operational templates Tbmax and primary drying time were also generated by simulation. The cycle run for the LDH formulation using the Edwards production dryer verified that the cycle developed in a laboratory freeze-dryer was transferable at the production scale.

Algorithms↗
PubMed2005

Practical formulation and process development of freeze-dried products.

Freeze-drying science and technology continues to evolve and increase in importance because of the emergence of biotechnology drugs that are too unstable to be commercially available as ready-to-use solutions. As more new drug compounds need to be developed as freeze-dried products, this mini-review article provides practical guidance and commentary on the latest literature articles on formulation and process development of freeze-dried products. This article contains a table that provides the quantitative formulations of all commercial freeze-dried protein pharmaceutical products through 2004.

Chemical Phenomena↗
PubMed2002

Excipient-drug interactions in parenteral formulations.

Excipients are added to parenteral formulations to enhance or maintain active ingredient solubility (solubilizers) and/or stability (buffers, antioxidants, chelating agents, cryo- and lyoprotectants). Excipients also are important in parenteral formulations to assure safety (antimicrobial preservatives), minimize pain and irritation upon injection (tonicity agents), and control or prolong drug delivery (polymers). These are all examples of positive or synergistic interactions between excipients and drugs. However, excipients may also produce negative effects such as loss of drug solubility, activity, and/or stability. This review article will highlight documented interactions, both synergistic and antagonistic, between excipients and drugs in parenteral formulations. The reader will gain better understanding and appreciation of the implications of adding formulation ingredients to parenteral drug products.

Animals↗