Novel dosage forms emerges more and more in recent years. One of them is liquid-filled hard gelatin capsules, which adopt gelatin or the hydroxypropyl methyl cellulose (HPMC) as capsule shell. The liquid-filled hard gelatin capsule is increasingly getting attention because of its new-concept dosage form design, which deliver liquid drugs by solid form. The paper mainly introduces application, pharmaceutical manufacturing, quality assessment, prospect of liquid-filled hard gelatin capsules, and focuses on the application and pharmaceutical manufacturing (preparation) of liquid-filled capsule. It is suggested that the capsule is suitable for various liquid or semi-solid natural plant extract and achieve different release profiles. The preparation adopted liquid-filled hard capsules technology. The influence factors concluded property of shell and device of filling. The quality was often evaluated by moisture content of capsule shell, dissolution rate etc. At the same time, it was pointed out that the new dosage form has remarkable marketing prospect and bring profits for enterprises.
Capsules ; chemistry ; Drug Delivery Systems ; Drugs, Chinese Herbal ; Gelatin ; chemistry

OBJECTIVETo study the dissolution characteristics of seven active components of Xianlinggubao capsules in vitro, and compare the dissolution of Xianlinggubao capsules prepared by different processes.

METHODThe dissolution of Xianlinggubao capsules was determined by small cup method with the rotating speed of 100 r x min(-1) and phosphate buffer (pH 6.8) as dissolution medium. The different dissolution rates in vitro of seven kinds of active components (icariin, epimedin C, asperosaponin VI, psoralen, isopsoralen, salvianolic acid B and tanshinone IIA) of Xianlinggubao capsules were investigated. The contents of active components were determined by HPLC. The accumulative dissolution percentages were calculated, and the resemblance of release curves were compared by similarity factors (f2).

RESULTThe results of determination showed that the similarity factor values (f2) of the dissolution curves of seven active components after different preparation processes were all less than 50.

CONCLUSIONThere is significant difference in dissolution of active components between Xianlinggubao capsules of different preparation processes. The accumulative dissolution percentages of the active components in new Xianlinggubao capsules are higher than that of Xianlinggubao capsules.

Capsules ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; Solubility

Taking guizhi fuling capsule (GZFL) for instance, a new method about reference Chinese medicine preparation which was used as standard substance for the quality evaluation of complex Chinese medicine preparation by the fingerprint of reference preparation instead of standard fingerprint was proposed. It could eliminate the errors from different instruments, chromatographic columns and solve the problem of similarity matching in the absence of standard fingerprint. The qualification of reference GZFL was evaluated according to the quality control method of GZFL from Chinese Pharmacopoeia. Then multiple batches of GZFL were estimated, taking fingerprint of reference preparation and standard fingerprint as references, respectively, at different instruments and chromatographic columns. Finally, the packaging and expiration date for reference GZFL were confirmed according to the results of stability investigation. The results indicated that the fingerprint of reference GZFL could be used to assess the quality of GZFL better than standard fingerprint. The data of accelerated stability and long-term stability test demonstrated that reference GZFL was stable in the conditions of double blister package. Therefore, reference GZFL can be used as standard substance in quality control of GZFL.
Capsules ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; standards ; Reference Standards

To control the risks of powder caking and capsule shell embrittlement of Guizhi Fuling Capsules, a predictive model for hygroscopicity of contents in Guizhi Fuling Capsules was built. A total of 90 batches of samples, including raw materials, intermediate powders and capsules, were collected during the manufacturing of Guizhi Fuling Capsules. According to the production sequence, 47 batches were used as the calibration set, and the properties of raw materials and the four intermediate powders were comprehensively characterized by the physical fingerprint. Then, the partial least squares(PLS) model was developed with the content hygroscopicity as the response variable. The variable importance in projection(VIP), variance inflation factor(VIF) and regression coefficients were used to screen out potential critical material attributes(pCMAs). As a result, five pCMAs from 54 physical parameters were screened out. Furthermore, different models were built by different combinations of pCMAs, and their predictive robustness of 43 batches was evaluated on the basis of the validation set. Finally, the tap density(D_c) of wet granules obtained from wet granulation and the angle of repose(α) of raw materials were identified as the critical material attributes(CMAs) affecting the hygroscopicity of the contents of Guizhi Fuling Capsules. The prediction model established with the two CMAs as independent variables had an average relative prediction error of 2.68% for samples in the validation set, indicating a good accuracy of prediction. This paper proved the feasibility of predictive modeling toward the control of critical quality attributes of Chinese medicine oral solid dosage(OSD). The combination of the continuous quality improvement, the industrial big data and the process modeling technique paved the way for the intelligent manufacturing of Chinese medicine oral solid preparations.
Capsules ; Drug Compounding ; Drugs, Chinese Herbal/chemistry* ; Powders ; Wettability

The effects of application of in-process quality control in Guizhi Fuling capsule production were evaluated by 192 batches data analysis. Using a statistical analysis method, each batch of data were to be counted to research for the difference between 96 samples adopting the technologies of in-process control or not. According to quality standards of Guizhi Fuling capsule, all measurements of the 192 batches of the drugs before and after the application of process control technology were analyzed, and they were within the rules. There was a significant difference between adopting the technologies of process control or not. Application of in-process control technology can improve the uniformity of lot-to-lot for Guizhi Fuling capsule.
Capsules ; chemistry ; Chemistry, Pharmaceutical ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Quality Control

The effects of ultrafine grinding on the dissolution rates of the effective components in Sanjie Zhentong capsule (SZC) were studied in this experiment. Fine and ultrafine powder of SZC intermediates were made by ordinary grinding and ultrafine grinding technology, and then granulated by wet granulation. SZC were prepared by fine powder, ultrafine powder and ultrafine granules, respectively. With resveratrol and loureirin B as investigated indexes, dissolution rates of the four intermediates in SZC were determined by cup method and HPLC. The dissolution rates of resveratrol in SZC prepared by fine powder, ultrafine powder and ultrafine granules were 26.11%, 63.27%, 67.49%, respectively; and the dissolution rates of loureirin B were 7.160%, 20.29%, 23.05%, respectively. The dissolution rate of resveratrol and loureirin B in SZC prepared by ultrafine granules was the best. D90 size of ultrafine grinding was 13.221 μm and could improve the dissolution rates of resveratrol and loureirin B in SZC.
Capsules ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Particle Size ; Silicones ; chemistry ; Solubility ; Technology, Pharmaceutical ; methods

In the present paper, the basic principles, the device and the analytical method of the hydrodynamic chromatography (HDC) were summarized, which is most widely used in hydrokinetic chromatography. The application of the hydrodynamic chromatography in the determination of the particle size and size distribution of the particulate drug delivery system was also reviewed. The method can determine the particle size of nano- and micron-scale particulate drug delivery systems rapidly. And this method also has the advantages of economic, convenient and no damage to the samples. In summary, there will be a good prospect for the application of HDC in the determination of particle size distribution features of particulate drug delivery systems.
Capsules ; chemistry ; Chromatography ; methods ; Drug Delivery Systems ; Hydrodynamics ; Liposomes ; chemistry ; Microspheres ; Nanoparticles ; chemistry ; Particle Size

OBJECTIVETo establish HPLC fingerprint of HQSM capsules,and a new method for correlativity analysis between fingerprint peaks of HQSM and its relevant herbs based on the fingerprint analysis.

METHODThe chromatographic fingerprints of HQSM and its relevant herbs were analyzed by HPLC configured with DAD. The similarity of the HPLC fingerprints between HQSM and its relevant herbs and the comparison of UV spectra of the main peaks in both of fingerprints were used as indices to evaluate the correlativity.

RESULTThe HPLC fingerprint with 16 common peaks was established and the chromatographic peaks were determined.

CONCLUSIONThe established method effectively controlled the quality of HQSM and establised the correlativity between HQSM and its relevant herbs, which would contribute to deduce the chemical components or sources of traditional Chinese medicine prescription.

Capsules ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo prepare gastric floating sustained-release formulation of Tripterygium wilfordii by using multiparticulate time-controlled release technology.

METHODThe intra-gastric floating blank-pellets were made by extrusion-spheronization method with 10% MCC as diluent and 90% cetylalcohol as floating assistant. The drug-loaded pellets were prepared in a fluid-bed coater with 1% HPMC, 0.5% SDS and extraction of T. wilfordii as coating solution. The gastric floating time-controlled release pellets were prepared with 3% L-HPC, 1% HPMC and 1% SDS as the inner swelling layer and ethylcellulose aqueous dispersion as the outer controlled layer. Finally, gastric floating sustained-release capsules of T. wilfordii were developed by encapsulating the five kinds of coated pellets whose coating load were 0%, 8%, 12%, 15% and 22% at equivalent ratio in hard gelatin capsules.

RESULTAfter formulation and coating load of swelling layer was fixed, the coated pellets would release active compositions in the different time expectably through regulating coating level of controlled layer. Several kinds of coated pellets whose controlled layer had different coating load were mixed and encapsulated into gastric floating sustained-release capsules of T. wilfordii. The capsules could float immediately in the dissolution medium and the floating rate of pellets was more than 80% in 8 h. The various kinds of coated pellets could release active compositions in accordance with time and show a characteristic of sustained-releasing as a whole.

CONCLUSIONThe gastric floating sustained-release capsules of T. wilfordii prepared by using multiparticulate time-controlled release technology have effective floating behavior and sustained release characteristics.

Capsules ; chemistry ; Chemistry, Pharmaceutical ; Delayed-Action Preparations ; chemistry ; Drug Delivery Systems ; methods ; Plant Extracts ; chemistry ; Tripterygium ; chemistry

OBJECTIVETo prepare a noisome formulation of Semen Strychni alkaloids extract with high encapsulation efficiency.

METHODS. Strychni alkaloids were encapsulated into niosomes by pH gradient loading method. The factors influencing on the encapsulation efficiency were investigated, and formulation and preparation process of niosomes were optimised and validated.

RESULTWhen the drug to lipid weight ratio was under 1: 10, pH gradient in buffer solution of citric acid at 50 degrees C was more than 4.0, the niosomes (mean diameter 179.2 nm and Zeta potential -25.41 mV) were formed with encapsulation efficiency of over 86.9%.

CONCLUSIONThe pH gradient loading method was reliable for preparing niosomes of Semen Strychni alkaloids extract.

Alkaloids ; chemistry ; Capsules ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; Hydrogen-Ion Concentration ; Liposomes ; chemistry ; Strychnos nux-vomica ; chemistry ; Temperature