| Along with the rapid development of the production technology of excipients,the pharmaceutical excipients with high chemical and physical stability,great compatibility,high inertness to other ingredients and patients and high cost-performance efficiency are becoming more and more popular.Meanwhile,with the creation of “Quality by Design(QbD)” concept,the importance of the functional parameters of excipients has been recognized during the formulation development of oral solid dosages.Firstly,this study will evaluate mannitol as a pharmaceutical excipient for oral solid dosage development both economically and technically in order to give scientific basis for the selection of excipients during formulation development.Because of the huge difference on the starting materials,manufacturing process and yield rate,the market price of mannitol is higher than that of traditional excipients such as lactose,MCC and sorbitol.It also should be noticed that the price and performance of crystalline mannitol,spray-dried mannitol and mannitol with different crystalline forms varies a lot.However,the inertness,safety and physical and chemical compatibility of mannitol is significantly better than those of other compared excipients.Its extremely low water content and hygroscopicity makes mannitol become the first choice for water sensitive API and dosage forms such as ODTs.Regarding its tableting properties,due to its high plasticity,mannitol can reduce tablets' sensitivity to the speed of the rotary press and improve the moldability of the formulation.Among the different grades of mannitol,spray-dried mannitol has better tableting properties with higher BET surface area.Its tableting properties can even be compared with MCC which is regarded as “dry binder”.Regarding the mouth feel,mannitol boasts cream-like texture,sweetness and refreshness which can improve the mouth feel of the final formulation.Therefore,it is very suitable to be used in dosage forms such as ODT,chewable tablet and sublingual tablet.Secondly,as by exposing one form of mannitol to high humidity,a water-induced polymorphic transition with the concurrent change in particle structure happens,it is proposed in this study that if these changes happen during a wet granulation process during preparation of oral solid dosage,it may cause a size reduction of mannitol with enhancement of compaction properties.PXRD and SEM confirmed that a polymorphic transition from ? form to ? form happens on wet-granulation,and that change led to ?-granule with needle-like fine primary crystals.The aim of this study was to evaluate the compression profile of ?-granule.The tablet compressed with ?-granules obtains a hardness of 2.5 times as high as that of the other mannitol samples.Heckel analysis shows that compression of mannitol caused by deformation without fragmentation and is particle size dependent.Because of its unique particle structure,?-granule showed enhanced plastic deformability.On the other hand,since the intrinsic compression profile of different polymorphs of mannitol were similar,primary particle size and BET surface area of mannitol were indicated to be the major factors for the improved compression profile,instead of the polymorphic transition itself.In order to confirm the conclusion of this study,vitamin C was used as a poorly compactable and high-dose model drug.By using ?-granule as filler,good tablets were prepared without any capping,while the other mannitol sample produced tablets with capping.Those founding indicates that ?-form mannitol powder has a huge potential to be used in the wet granulation process.Also pre-granulated ?-form mannitol can be used in direct compression process and dry granulation process.In summary,different grades and crystalline forms of mannitol has a high value and huge potential in the area of direct compression and granulation process within the production of oral solid dosages. |
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