If the goal of clustering is to try and get clusters that recover as much as possible drug indications then I would simply go for the clustering with the best [purity] relative to indication. To define a statistically significant enrichment you need to set a p-value threshold (and don't forget to account for multiple testing). However having a p-value for each cluster doesn't help in comparing clustering methods since it doesn't tell you about effect size (i.e. how many drugs of a given class is in a cluster). In a hypothetical example, you could have a cluster with five drugs with indication A and two drugs with indication B and the enrichment test returning indication B as significantly enriched but not A.