Development of platform technology for gastro-resistant soft gel capsules by using the cross-linking technique

Introduction: Conventional enteric coating is very challenging in soft gel capsules because of shell nature (smooth surfaces and elasticity). Soft gelatin capsules are highly sensitive to temperature, humidity and it can lose their tensile strength during the conventional coating process. Materials and Methods: Enteric soft gel capsules were prepared by addition of enteric polymer in the gelatin shell composition by inducing the cross linking of gelatin through chemical treatment. Results: This dual approach makes the soft gelatin capsules to resist the drug release in stomach and reliably release their contents in the intestine within a predetermined time without affecting the physical properties of soft gel capsules. Conclusions: Enteric effect of soft gel capsules are brought by a specialized synergetic technique which is unique for the molecules which need intestinal drug release.

Pathways for Oral and Rectal Delivery of Gold Nanoparticles (1.7 nm) and Gold Nanoclusters into the Colon: Enteric-Coated Capsules and Suppositories

Two ways to deliver ultrasmall gold nanoparticles and gold-bovine serum albumin (BSA) nanoclusters to the colon were developed. First, oral administration is possible by incorporation into gelatin capsules that were coated with an enteric polymer. These permit the transfer across the stomach whose acidic environment damages many drugs. The enteric coating dissolves due to the neutral pH of the colon and releases the capsule’s cargo. Second, rectal administration is possible by incorporation into hard-fat suppositories that melt in the colon and then release the nanocarriers. The feasibility of the two concepts was demonstrated by in-vitro release studies and cell culture studies that showed the easy redispersibility after dissolution of the respective transport system. This clears a pathway for therapeutic applications of drug-loaded nanoparticles to address colon diseases, such as chronic inflammation and cancer.

Formulation and invitro evaluation of delayed release multiple unit pellets of Lansoprazole in capsules

The present research was aimed to formulate and evaluate Lansoprazole delayed release multiple unit pellets in capsules. Lansoprazole degrades in the acidic environment of the stomach. It is also unstable under conditions of high temperature and high humidity which leads to therapeutic inefficiency. Hence it is important to bypass the acidic pH of the stomach. Protection of drug from acidic environment is done by coating the drug with enteric polymer. In the present study, successive layers of drug layer, barrier layer and enteric layer was coated on the inert sugar spheres by using solution/suspension layering technique in Fluidized bed processor (FBP). The prepared drug layered and barrier layered pellets were evaluated for % yield. The prepared lubricated pellets were evaluated for flow properties i.e., bulk density, tapped density, compressibility index and hausner’s ratio. Lubricated pellets filled into size ‘1’ capsules and evaluated for drug content, drug content resisted in acid, invitro drug release studies and compared with the marketed product. The dissimilarity and similarity factors for the optimized and marketed formulations were found to be 84.29. Accelerated Stability Testing (AST) was performed as per the ICH guidelines at 40±5°C/75±5% RH for 6 months and found satisfactory.

Toward Mechanistic Design of Surrogate Buffers for Dissolution Testing of pH-Dependent Drug Delivery Systems

The in vivo dissolution of enteric-coated (EC) products is often overestimated by compendial in vitro dissolution experiments. It is of great interest to mimic the in vivo conditions as closely as possible in vitro in order to predict the in vivo behavior of EC dosage forms. The reason behind this is the overly high buffering capacity of the common compendial buffers compared to the intestinal bicarbonate buffer. However, a bicarbonate-based buffer is technically difficult to handle due to the need for continuous sparging of the media with CO2 to maintain the desired buffer pH. Therefore, bicarbonate buffers are not commonly used in routine practice and a non-volatile alternative is of interest. A mathematical mass transport modelling approach was previously found to enable accurate calculation of surrogate buffer molarities for small molecule compounds; however, the additional complexity of polymeric materials makes this difficult to achieve for an enteric coat. In this work, an approach was developed allowing relatively rapid screening of potential surrogate buffers for enteric coating. It was found that the effective buffering pKa of bicarbonate at the surface of a dissolving enteric polymer tended to be around 5.5, becoming higher when the dissolving enteric polymer formed a gel of greater firmness/viscosity and vice versa. Using succinate (pKa 5.2 under physiological ionic strength) and/or citrate (pKa 5.7 under physiological ionic strength) at conjugate base molarities corresponding to bicarbonate molarities in the intestinal segments of interest as an initial “guess” can minimize the number of experimental iterations necessary to design an appropriate surrogate.

In Vitro Evaluation of Enteric-Coated HPMC Capsules—Effect of Formulation Factors on Product Performance

A comparative study on different enteric-coated hard capsules was performed. The influence of different formulation factors like choice of enteric polymer, triethyl citrate (TEC) concentration (plasticizer), talc concentrations (anti-tacking agent), and different coating process parameters on the sealing performance of the capsule and the disintegration time were investigated. Furthermore, the influence of different disintegration test methods (with disc vs. without disc and 50 mM U.S. Pharmacopoeia (USP) buffer pH 6.8 vs. biopredictive 15 mM phosphate buffer pH 6.5) was evaluated. All formulations showed sufficient but not equivalent acid resistance when tested. Polymer type was the main factor influencing the capsule sealing and disintegration time. In addition, TEC and talc could affect the performance of the formulation. Regarding the choice of the disintegration test method, the presence of a disc had for the most part only limited influence on the results. The choice of disintegration buffer was found to be important in identifying differences between the formulations.