Manufacturing Of Pharmaceutical Dosage Forms Research Articles

Investigating the Use of Magnetic Nanoparticles As Alternative Sintering Agents in Selective Laser Sintering (SLS) 3D Printing of Oral Tablets.

Selective laser sintering (SLS) is a single-step, three-dimensional printing (3DP) process that is gaining momentum in the manufacturing of pharmaceutical dosage forms. It also offers opportunities for manufacturing various pharmaceutical dosage forms with a wide array of drug delivery systems. This research aimed to introduce carbonyl iron as a multifunctional magnetic and heat conductive ingredient for the fabrication of oral tablets containing isoniazid, a model antitubercular drug, via SLS 3DP process. Furthermore, the effects of magnetic iron particles on the drug release from the SLS printed tablets under a specially designed magnetic field was studied. Optimization of tablet quality was performed by adjusting SLS printing parameters. The independent factors studied were laser scanning speed, hatching space, and surface/chamber temperature. The responses measured were printed tablets' weight, hardness, disintegration time, and dissolution performance. It has been observed that, for the drug formulation with carbonyl iron, due to its inherent thermal conductivity, sintering tablets required relatively lower laser energy input to form the tablets of the same quality attributes as the other batches that contained no magnetic particles. Also, printed tablets with carbonyl iron released 25% more drugs under a magnetic field than those without it. It can be claimed that magnetic nanoparticles appear as an alternative conductive material to facilitate the sintering process during SLS 3DP of dosage forms.

3D screen printing – An innovative technology for large-scale manufacturing of pharmaceutical dosage forms

Three-dimensional (3D) screen printing was used to fabricate oral dosage forms of different geometry and size. The paste required as starting material for the 3D screen printing process was designed for delayed release and contained the model drug paracetamol (acetaminophen). A prototype screen printing unit was used to fabricate different tablets in a single production process. The resulting tablets were produced with three different sizes and designed geometries (disk, donut, cuboid, oval and grid). Investigation of size and mass of the individual tablets demonstrated high uniformity within the various groups of tablets. Further characterization of their physical properties, such as breaking force and friability, yielded results comparing favorably to conventionally produced tablets. Finally, drug release tests in artificial gastric media showed paracetamol release to depend on the surface-area-to-volume ratio. In conclusion, the study shows the potential of 3D screen printing to fabricate more complex oral dosage forms in the setting of mass production with high reproducibility.

A Review on Pharmaceutical Process Validation

The process validation is one of the most essential key factor when it comes to the efficient manufacturing of pharmaceutical dosage forms. The process validation assures the highest degree of uniform results and also helps to meet the predefined specifications for the dosage form. Also process validation assures the quality of the product and helps to meet desired results. It basically involves the collection and analyzing the data from product design stage which ensures that the process is capable for the production of quality product. Through this review article we want to have had the knowledge of the process validation and also want to put the basic outline over this process validation process.

Rapid automated process development of a continuous capsule-filling process

This paper introduces a rapid automated process-development approach for a continuous capsule-filling process. In our proposed method, both the material attributes and the critical process parameters were varied to understand and to optimize the overall process. Using our approach a statistical process model can be generated with unprecedented speed (2 days), which is the prerequisite for effectively developing and operating continuous process platforms. In a first set of experiments a process model was developed using different mixture compositions of ascorbic acid, lactose and magnesium stearate while changing simultaneously the critical process parameters of the capsule filler (speed, pressure, immersion depth and powder bed height). Targets of the model were the mean fill weight and the relative standard deviation of the produced capsules. In a second experimental set the model was tested, i.e., the goal was to predict the behavior of the system at different set points in order to predict weight and relative standard deviation for predefined targets. Predictions were very good, thus validating our approach. The combination of the rapid automated process development approach and the continuous capsule-filling process resulted in a new strategy for the development and manufacture of pharmaceutical dosage forms.

Cocrystallization by Freeze-Drying: Preparation of Novel Multicomponent Crystal Forms

We demonstrate the utility of freeze-drying as a general method for cocrystal synthesis as well as for the preparation of new solid forms of drug–coformer cocrystal systems. Using this approach, several previously reported cocrystal phases containing pharmaceutical compounds were reproduced. In addition, a novel solid solution of caffeine and theophylline and a potential new crystal form of the theophylline:oxalic acid cocrystal were prepared. It is shown that cocrystal formation proceeds via an amorphous phase that is generated as solvent sublimes during the freeze-drying process. The application of freeze-drying to cocrystallization is advantageous as it avoids problems caused by differences in the solubilities of coformers and is a technique that is widely used to prepare products on an industrial scale, such as in the manufacture of pharmaceutical dosage forms.

Professor Michael J. Pikal: Scientist, family man, educator, colleague and friend

Professor Michael J. Pikal: Scientist, family man, educator, colleague and friend

The impact of primary packaging on the quality of parenteral products

The unique approach in manufacturing of pharmaceutical dosage forms of active substances known to be unstable in aqueous solution is the introduction of lyophilization process. Nevertheless, these products must be reconstituted using the diluent from a separate container before application. The possible solution for this problem is the application of dual chamber vials comprising the freeze-dried product in a lower compartment of the vial and the solution for reconstitution in the upper chamber. The main issue in development of such product is the choice of contact packaging (rubber closures, glass vials and the container closure system as a whole). The most important parameter used for evaluation of the influence of contact material on product quality was the pH value. The results have shown that the type of vials (moulded or tubular glass) has no impact on pH shift of the solution for reconstitution (tested solution—TS), while significant differences in pH value of the TS were observed depending on the rubber closures formulation used (with some formulations, the pH shift during the test was 6.5–9.14). Benzyl alcohol assay during the tests remained unchanged. Integrity tests of the container closure system (CCS) have demonstrated the adequacy of the selected packaging system. The quality of the CCS of choice was confirmed in the course of stability studies, only parameters directly influenced by CCS being presented in this work: loss on drying and pH value. On the basis of these results, no changes in loss on drying were connected to CCS, and the pH value of the reconstituted solution remains unchanged in samples tested both ex-tempore and after in-use period of 48 h.

Continuous granulation in the pharmaceutical industry

Traditionally the manufacturing of pharmaceutical dosage forms has been a batch-wise process and continuous processes have limited applications in a pharmaceutical manufacturing plant. However, several factors (reduction of cost, improved process efficiency, optimal use of equipment, flexibility in production capacity) are stimulating the pharmaceutical industry to investigate the opportunities offered by continuous processes. This paper discusses some of the techniques which could be implemented in a continuous granulation process of pharmaceuticals.

Thermal analysis of spray dried products

Abstract The ability to alter and control such properties as particle shape, particle size and size distribution, bulk density, porosity, moisture content, flowability, stability, dispersability and friability has led to the increasing use over the last fifty years, of spray drying methods in the manufacture of pharmaceutical dosage forms. However, in addition to the above changes, alterations may also occur in the energy of the spray dried solid components ranging from the disordering of the crystal lattice, the formation of polymorphic and/or pseudopolymorphic forms, the elimination of crystallinity to complex formation. These changes can have far reaching effects on the biopharmaceutical properties and stability of the dosage forms. In this paper reports of such changes occurring in pharmaceutical systems are reviewed and in particular the use of thermal analytical methods to both qualitatively and quantitatively evaluate the occurrence of these solid state modifications.