Investigation of various factors affecting encapsulation on the In-Cap automatic capsule-filling machine

Abstract

The purpose of this study was to determine the factors that influence fill weight and weight variability of capsules produced on the In-Cap and to assess any differences in terms of capsule defects between gelatin and HPMC (Quali-V) shells. The In-Cap is an automatic tamping type capsule-filling machine and the low output of ~3000 capsules/hour makes it ideal for early formulation development and phase I/IIa clinical supplies manufacture. Four commonly used excipients (Avicel PH101, Avicel PH302, A-Tab, and Prosolv HD90) and a poorly flowing drug blend were encapsulated at various pin settings and powder bed heights. The average fill weight and coefficient of weight variation were determined. The percentage of defective capsules formed during encapsulation was calculated. Results of the study showed that pin setting was critical for controlling the fill weight and the weight variation. The order of pin setting with pin 1 (closer to the powder chute) set to a relatively higher position and pin 4 (before ejection) set to a lower position was found to give higher fill weights with relatively lower weight variability. The powder bed height influenced the fill weight for poorly flowing powders. The capsule machine speed did not appear to significantly influence the fill weight. The fill weight and weight variation were found to depend on the flow property of the material. A large percentage of defective capsules was obtained using HPMC shell size #00. Some of the commonly observed defects included split caps and improperly closed filled capsules. In general, appropriate selection of pin settings and bed height can reduce the weight variability seen, especially with poorly flowing high-dose formulations.

Development and Characterisation of Modified Release Hard Gelatin Capsules, Based on In Situ Lipid Matrix Formation

“…Based on the loss of drying results, we can state that our capsules were stored appropriately and they were fully suitable for our experiments (35). Additionally, our experiment was rather unique by applying short-term heating to the empty shells and measuring the remaining water content.…”

“…closed in fully filled containers or humidified hot air as heating medium, is applied. However, when wet air is applied, deformation and sticking of the capsules can occur (35,37). Among critical process parameters, we can mention the high degree of homogeneity of the powder mixture (necessary to develop uniform matrices in shape and strength).…”

Commercially Available Enteric Empty Hard Capsules, Production Technology and Application

“…The drug is encapsulated here as a mixture of different excipients to the hard capsule, consisting of a lower part (body) into which the mixture is filled and closed with an upper part of the capsule (cap). Laboratory machines (manual capsule filling machines) [4,5] or semi-automatic alternatively automatic devices (capsule filling machines) [1,3,6] are usually used for encapsulation in pharmacies or research fields. Materials used for manufacturing both capsule parts are often dried glycerogelatin or, more recently, cellulose derivates, mostly hydroxypropyl methylcellulose (HPMC) or other derivatives, and different hydrophilic polymers.…”

To investigate the influence of machine operating variables on formulations derived from lactose types in capsule filling: part 2

“…For example, capsules can sometimes make the formulation of poorly compressible high dose drugs easier by avoiding the need for wet granulation and its associated cost and stability problems 8,9 . Capsule dosage forms are often preferred by the pharmaceutical industry for phase I and phase II clinical study as they are simpler and quicker to develop compared to tablets 10 . In some surveys, capsule dosage forms are favored over other types 11,12 .…”