Two drug molecules, Propranolol and Persantin, have been encapsulated by a sol gel process in an organic-inorganic hybrid matrix by in-situ self-assembly. The synthesis parameter, compositions and pH values in the sol-gel synthesis controls the dissolution of the drugs, and pore size and distribution of the gels. The main difference between an ordinary physical encapsulation and a structure directing role of the guest molecule on the matrix genesis critically depends on the strengths, selectivities and cooperativities of non-covalent host-guest interactions. The local molecular interaction between the drug and the host matrix has been investigated by employing two-dimensional heteronuclear correlation NMR spectroscopy. The results from the NMR studies provide deeper insights into the molecular level interactions between the host and the guest which will help us to design better materials for controlled drug release.